Introduction: Plasmodium falciparum has the ability to counter the antiparasitic activity of sulphadoxine-pyrimethamine by progressively accumulating mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes. These mutations gradually increase the resistance of the parasite to these drugs and lead to therapeutic failure.
Objectives: To determine the frequency of mutations associated with resistance to sulphadoxine and pyrimethamine in the dhfr and dhps genes of P. falciparum in samples from patients in three endemic zones of Colombia -La Carpa, Guaviare; Casuarito, Vichada; and Tierralta and Puerto Libertador, Córdoba.
Materials And Methods: Forty samples were selected from patients with uncomplicated P. falciparum malaria. The frequency profiles of the 108, 59 and 164 alleles of dhfr were obtained by application of an allele-specific polymerase chain reaction, whereas the other alleles (alleles 51 of the dhfr gene and 436, 437 and 540 of dhps) were obtained by polymerase chain reaction and restriction fragment length polymorphism.
Results: The 108N and 51I mutations in the dhfr gene were found in all of the 40 samples. No mutant alleles were found in the 59 and 164 codons of the dhfr gene, or in the 436 codon of the dhps gene. The 437G mutation was observed in 36 samples and the wild-type allele was present in 3 from Tierralta and one from La Carpa. The 540E mutation was only detected in two samples from Casuarito.
Conclusions: The 108N, 51I and 437G mutations prevail in the populations of P. falciparum, indicating a cumulative effect of mutations and the need to continue surveillance for other changes which can lead to the total loss of the efficacy of sulphadoxine-pyrimethamine.
Download full-text PDF |
Source |
---|
Infect Drug Resist
December 2024
Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.
Purpose: pneumonia (PJP) shows a high fatality rate in non-HIV patients. However, there are limited data on drug resistance-related gene mutations in these patients. This study aimed to describe the prevalence of mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of in non-HIV patients in China, providing a reference for drug usage.
View Article and Find Full Text PDFStructure
December 2024
Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark. Electronic address:
Gene variants resulting in insertions or deletions of amino acid residues (indels) have important consequences for evolution and are often linked to disease, yet, compared to missense variants, the effects of indels are poorly understood and predicted. We developed a sensitive protein folding sensor based on the complementation of uracil auxotrophy in yeast by circular permutated orotate phosphoribosyltransferase (CPOP). The sensor reports on the folding of disease-linked missense variants and de-novo-designed proteins.
View Article and Find Full Text PDFWellcome Open Res
June 2024
MARCAD Program, The biotechnology Centre, University of Yaounde I, Yaounde, Centre, P 0 Box 8094, Cameroon.
Background: Antimalarial drug resistance is a major challenge in the fight against malaria. Cameroon implemented seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SPAQ) to over 1.5 million children aged 3-59 months from 2016, raising concerns whether drug pressure may lead to a selection of known parasite resistance mutations.
View Article and Find Full Text PDFVet Parasitol Reg Stud Reports
November 2024
Warnell School of Forestry and Natural Resources, 180 E Green Street, University of Georgia, Athens, GA 30602, USA; Southeastern Cooperative Wildlife Disease Study, 589 D.W. Brooks Drive, Wildlife Health Building, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, USA; Center for the Ecology of Infectious Diseases, University of Georgia, Athens, GA 30602, USA. Electronic address:
Trypanosoma cruzi is an important cause of disease and death in humans and dogs, and although wildlife infections are common, less is known about disease manifestations. A 12-week-old male American black bear (Ursus americanus) cub with mild lethargy and anorexia presented to a wildlife rehabilitation center in Lake Tahoe, California. The cub continued to become increasingly weak and showed decreasing interest in play and other activities.
View Article and Find Full Text PDFBiochem Pharmacol
December 2024
Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, United States. Electronic address:
Cellular resistance can limit the effectiveness of antifolate drugs for the treatment of cancer and autoimmune diseases. We examined the biochemical and cellular effects of a propargyl linked, non-classical antifolate UCP1162 that shows exceptional potency and resilience in the background of methotrexate resistance. UCP1162 inhibited the human DHFR enzyme with affinity and kinetics comparable to methotrexate (MTX).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!