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Genome-wide association studies unveil major genetic loci driving insecticide resistance in Anopheles funestus in four eco-geographical settings across Cameroon.
BMC Genomics
December 2024
Centre for Research in Infectious Diseases (CRID), P.O. BOX 13591, Yaoundé, Cameroon.
Background: Insecticide resistance is jeopardising malaria control efforts in Africa. Deciphering the evolutionary dynamics of mosquito populations country-wide is essential for designing effective and sustainable national and subnational tailored strategies to accelerate malaria elimination efforts. Here, we employed genome-wide association studies through pooled template sequencing to compare four eco-geographically different populations of the major vector, Anopheles funestus, across a South North transect in Cameroon, aiming to identify genomic signatures of adaptive responses to insecticides.
View Article and Find Full Text PDFmolecular surveillance to inform the Mozambican National Malaria Control Programme strategy: protocol.
BMJ Open
November 2024
Centro de Investigação em Saúde de Manhiça (CISM), Manhiça, Mozambique
Introduction: Malaria molecular surveillance has the potential to generate information on biological threats that compromise the effectiveness of antimalarial interventions. This study aims to streamline surveillance activities to inform the new strategic plan of the Mozambican National Malaria Control Programme (2023-2030) for malaria control and elimination.
Methods And Analyses: This prospective genomic surveillance study aims to generate genetic data to monitor diagnostic failures due to deletions and molecular markers of antimalarial drug resistance, to characterise transmission sources and to inform the implementation of new antimalarial approaches to be introduced in Mozambique (chemoprevention and child malaria vaccination).
Accelerating Antimalarial Drug Discovery with a New High-Throughput Screen for Fast-Killing Compounds.
ACS Infect Dis
December 2024
Department of Molecular Infection Dynamics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki 852-8523, Japan.
The urgent need for rapidly acting compounds in the development of antimalarial drugs underscores the significance of such compounds in overcoming resistance issues and improving patient adherence to antimalarial treatments. The present study introduces a high-throughput screening (HTS) approach using 1536-well plates, employing lactate dehydrogenase (PfLDH) combined with nitroreductase (NTR) and fluorescent probes to evaluate inhibition of the growth of the asexual blood stage of malaria parasites. This method was adapted to efficiently assess the speed of action profiling (SAP) in a 384-well plate format, streamlining the traditionally time-consuming screening process.
View Article and Find Full Text PDFApplication of a new highly multiplexed amplicon sequencing tool to evaluate antimalarial resistance and relatedness in individual and pooled samples from Dschang, Cameroon.
medRxiv
October 2024
Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Background: Resistance to antimalarial drugs remains a major obstacle to malaria elimination. Multiplexed, targeted amplicon sequencing is being adopted for surveilling resistance and dissecting the genetics of complex malaria infections. Moreover, genotyping of parasites and detection of molecular markers drug resistance in resource-limited regions requires open-source protocols for processing samples, using accessible reagents, and rapid methods for processing numerous samples including pooled sequencing.
View Article and Find Full Text PDFA Divergent Synthesis of Numerous Pyrroloiminoquinone Alkaloids Identifies Promising Antiprotozoal Agents.
J Am Chem Soc
October 2024
Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697, United States.
Article Synopsis
- * The key step in our synthesis employed a Larock indole synthesis, allowing us to create a significant intermediate that could be further modified through selective methylation and other transformations.
- * Our testing of these compounds showed promising low toxicity towards human cells, alongside potent activity against malaria and related protozoan parasites, indicating their potential as candidates for drug development.
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