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Modified dosing schedule efficacy of fosmidomycin and clindamycin against murine malaria Plasmodium berghei.
Int J Parasitol Drugs Drug Resist
December 2024
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD, 21210, USA. Electronic address:
Fosmidomycin and clindamycin target the Plasmodium apicoplast. Combination clinical trials have produced mixed results with the primary problem being the recrudescent infection frequency by day 28. Given that antibiotic efficacy against bacterial infections often depends on the constant drug presence over several days, we hypothesized that the antimalarial blood or liver stage efficacy of fosmidomycin and clindamycin could be improved by implementing a more frequent dosing schedule.
View Article and Find Full Text PDFProtective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein.
Science
January 2025
Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
The most advanced monoclonal antibodies (mAbs) and vaccines against malaria target the central repeat region or closely related sequences within the circumsporozoite protein (PfCSP). Here, using an antigen-agnostic strategy to investigate human antibody responses to whole sporozoites, we identified a class of mAbs that target a cryptic PfCSP epitope that is only exposed after cleavage and subsequent pyroglutamylation (pGlu) of the newly formed N terminus. This pGlu-CSP epitope is not targeted by current anti-PfCSP mAbs and is not included in the licensed malaria vaccines.
View Article and Find Full Text PDFThe antimalarial activity of transdermal N-89 mediated by inhibiting ERC gene expression in P. Berghei-infected mice.
Parasitol Int
December 2024
Division of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan. Electronic address:
Through studies of new antimalarial drugs, we identified 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) as a potential drug candidate. Here, we analyzed the antimalarial action of a transdermal formulation (td) of N-89, designed for easy use by children, using Plasmodium berghei-infected mice as a model for malaria patients.
View Article and Find Full Text PDFGeneration of a genetically double-attenuated Plasmodium berghei parasite that fully arrests growth during late liver stage development.
PLoS One
December 2024
Institute of Cell Biology, University of Bern, Bern, Switzerland.
Malaria caused by Plasmodium parasites remains a large health burden. One approach to combat this disease involves vaccinating individuals with whole sporozoites that have been genetically modified to arrest their development at a specific stage in the liver by targeted gene deletion, resulting in a genetically attenuated parasite (GAP). Through a comprehensive phenotyping screen, we identified the hscb gene, encoding a putative iron-sulfur protein assembly chaperone, as crucial for liver stage development, making it a suitable candidate gene for GAP generation.
View Article and Find Full Text PDFModulation of 8-Oxoguanine DNA Glycosylase 1 (OGG1) Alleviated Anemia Severity and Excessive Cytokines Release during Malaria in Mice.
Iran J Parasitol
January 2024
Department of Pre-Clinical, Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur, Malaysia.
Background: The interplay of OGG1, 8-Oxoguanine, and oxidative stress triggers the exaggerated release of cytokines during malaria, which worsens the outcome of the disease. We aimed to investigate the involvement of OGG1 in malaria and assess the effect of modulating its activity on the cytokine environment and anemia during malaria in mice.
Methods: infection in ICR mice was used as a malaria model.
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