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Clinical and In Vitro Resistance of Plasmodium falciparum to Artesunate-Amodiaquine in Cambodia.
Clin Infect Dis
August 2021
Malaria Molecular Epidemiology Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia.
Background: Artesunate-amodiaquine is a potential therapy for uncomplicated malaria in Cambodia.
Methods: Between September 2016 and January 2017, artesunate-amodiaquine efficacy and safety were evaluated in a prospective, open-label, single-arm observational study at health centers in Mondulkiri, Pursat, and Siem Reap Provinces, Cambodia. Adults and children with microscopically confirmed Plasmodium falciparum malaria received oral artesunate-amodiaquine once daily for 3 days plus single-dose primaquine, with follow-up on days 7, 14, 21, and 28.
Amodiaquine resistance in is associated with His95Pro mutation, loss of chloroquine, artemisinin and primaquine sensitivity, and high transcript levels of key transporters.
Wellcome Open Res
June 2017
Department of Biochemistry, Jomo Kenyatta University of Agriculture and Technology, Nairobi, 00200, Kenya.
The human malaria parasite has evolved complex drug evasion mechanisms to all available antimalarials. To date, the combination of amodiaquine-artesunate is among the drug of choice for treatment of uncomplicated malaria. In this combination, a short acting, artesunate is partnered with long acting, amodiaquine for which resistance may emerge rapidly especially in high transmission settings.
View Article and Find Full Text PDFA cross-sectional survey of Plasmodium falciparum pfcrt mutant haplotypes in the Democratic Republic of Congo.
Am J Trop Med Hyg
June 2014
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina; Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina; Department of Geography, University of North Carolina, Chapel Hill, North Carolina; Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina; Ecole de Sante Publique, Faculte de Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.
In the Democratic Republic of the Congo (DRC), artesunate-amodiaquine is first-line therapy for falciparum malaria; little is known about the prevalence of molecular markers of parasite drug resistance. Across the DRC, we genotyped 166 parasites in Plasmodium falciparum chloroquine resistance transporter (pfcrt) using polymerase chain reaction (PCR) and sequencing. Of these parasites, 73 (44%) parasites were pure wild-type CVMNK, 55 (31%) parasites were chloroquine-resistant CVIET: , 35 (21.
View Article and Find Full Text PDFSome features of primary and recrudescent amodiaquine-resistant Plasmodium falciparum infections in Nigerian children.
Mem Inst Oswaldo Cruz
December 2008
Department of Pharmacology and Therapeutics, Institute for Medical Research and Training, University of Ibadan, Ibadan, Nigeria.
Characteristics of primary and recrudescent Plasmodium falciparum infections were evaluated in 25 children who did not recover after amodiaquine (AQ) treatment. Recrudescence was detected by a thick blood smear and confirmed by polymerase chain reaction. Over half of recrudescent events occurred after 14 days of initiation of treatment and were associated with relatively low asexual parasitaemia.
View Article and Find Full Text PDFAmodiaquine resistant Plasmodium falciparum malaria in vivo is associated with selection of pfcrt 76T and pfmdr1 86Y.
Infect Genet Evol
July 2006
Malaria Research Laboratory, Unit of Infectious diseases, Department of Medicine, Karolinska Institute, Karolinska University Hospital, M9:02, 17176 Stockholm, Sweden.
The choice of partner drug is critical for artemisinine-based combination therapy (ACT) to remain effective and amodiaquine (AQ) is one important candidate to evaluate. We treated 81 children <5 years with uncomplicated Plasmodium falciparum malaria with AQ alone and related the treatment outcome to the possible selection of pfcrt 76T, 152T, 163S, 326S, pfmdr1 86Y and pfmrp 191H, 437S in recurrent infections (recrudescenses and re-infections) and to the blood concentration of desethylamodiaquine (DEAQ). During 21 days follow-up 28 children had a recurrent infection (9 recrudescenses, 13 re-infections and 6 mixed).
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