scholarly journals Baseline Ex Vivo and Molecular Responses of Plasmodium falciparum Isolates to Piperaquine before Implementation of Dihydroartemisinin-Piperaquine in Senegal

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Marie Gladys Robert ◽  
Francis Foguim Tsombeng ◽  
Mathieu Gendrot ◽  
Silman Diawara ◽  
Marylin Madamet ◽  
...  

ABSTRACT Dihydroartemisinin-piperaquine, which was registered in 2017 in Senegal, is not currently used as the first-line treatment against uncomplicated malaria. A total of 6.6% to 17.1% of P. falciparum isolates collected in Dakar in 2013 to 2015 showed ex vivo-reduced susceptibility to piperaquine. Neither the exonuclease E415G mutation nor the copy number variation of the plasmepsin II gene (Pfpm2), associated with piperaquine resistance in Cambodia, was detected in Senegalese parasites.

2013 ◽  
Vol 57 (11) ◽  
pp. 5277-5283 ◽  
Author(s):  
Pharath Lim ◽  
Dalin Dek ◽  
Vorleak Try ◽  
Richard T. Eastman ◽  
Sophy Chy ◽  
...  

ABSTRACTIn 2008, dihydroartemisinin (DHA)-piperaquine (PPQ) became the first-line treatment for uncomplicatedPlasmodium falciparummalaria in western Cambodia. Recent reports of increased treatment failure rates after DHA-PPQ therapy in this region suggest that parasite resistance to DHA, PPQ, or both is now adversely affecting treatment. While artemisinin (ART) resistance is established in western Cambodia, there is no evidence of PPQ resistance. To monitor for resistance to PPQ and other antimalarials, we measured drug susceptibilities for parasites collected in 2011 and 2012 from Pursat, Preah Vihear, and Ratanakiri, in western, northern, and eastern Cambodia, respectively. Using a SYBR green I fluorescence assay, we calculated theex vivo50% inhibitory concentrations (IC50s) of 310 parasites to six antimalarials: chloroquine (CQ), mefloquine (MQ), quinine (QN), PPQ, artesunate (ATS), and DHA. Geometric mean IC50s (GMIC50s) for all drugs (except PPQ) were significantly higher in Pursat and Preah Vihear than in Ratanakiri (P≤ 0.001). An increased copy number ofP. falciparummdr1(pfmdr1), an MQ resistance marker, was more prevalent in Pursat and Preah Vihear than in Ratanakiri and was associated with higher GMIC50s for MQ, QN, ATS, and DHA. An increased copy number of a chromosome 5 region (X5r), a candidate PPQ resistance marker, was detected in Pursat but was not associated with reduced susceptibility to PPQ. Theex vivoIC50andpfmdr1copy number are important tools in the surveillance of multidrug-resistant (MDR) parasites in Cambodia. While MDRP. falciparumis prevalent in western and northern Cambodia, there is no evidence for PPQ resistance, suggesting that DHA-PPQ treatment failures result mainly from ART resistance.


2013 ◽  
Vol 57 (7) ◽  
pp. 3412-3414 ◽  
Author(s):  
Jérome Dormoi ◽  
Sébastien Briolant ◽  
Camille Desgrouas ◽  
Bruno Pradines

ABSTRACTAlthough 100% of untreated mice infected withPlasmodium bergheidied with specific signs of cerebral malaria and 100% of mice treated with 3 mg/kg dihydroartemisinin, the active metabolite of artesunate, which is used as the first-line treatment for severe malaria, also died but showed no specific signs of cerebral malaria, 78% of mice treated with 10 mg/kg Proveblue (methylene blue) and 78% of mice treated with a combination of 3 mg dihydroartemisinin and 10 mg/kg Proveblue survived and showed no specific signs of cerebral malaria or detectable parasites.


2007 ◽  
Vol 52 (2) ◽  
pp. 739-741 ◽  
Author(s):  
Zhiyong Zhou ◽  
Sean M. Griffing ◽  
Alexandre Macedo de Oliveira ◽  
Andrea M. McCollum ◽  
Wilmer Marquino Quezada ◽  
...  

ABSTRACT The frequency of alleles with triple mutations conferring sulfadoxine-pyrimethamine (SP) resistance in the Peruvian Amazon Basin has declined (16.9% for dhfr and 0% for dhps compared to 47% for both alleles in 1997) 5 years after SP was replaced as the first-line treatment for Plasmodium falciparum malaria. Microsatellite analysis showed that the dhfr and dhps alleles are of common origin.


2015 ◽  
Vol 59 (8) ◽  
pp. 4417-4423 ◽  
Author(s):  
Tamalee Roberts ◽  
Stephen Bush ◽  
John Ellis ◽  
John Harkness ◽  
Damien Stark

ABSTRACTBlastocystisis the most common human enteric protist with controversial clinical significance. Metronidazole is considered a first-line treatment forBlastocystisinfection; however, there has been increasing evidence for the lack of efficacy of this treatment. Treatment failure has been reported in several clinical cases, and recentin vitrostudies have suggested the occurrence of metronidazole-resistant strains. In this study, we tested 12Blastocystisisolates from 4 commonBlastocystissubtypes (ST1, ST3, ST4, and ST8) against 12 commonly used antimicrobials (metronidazole, paromomycin, ornidazole, albendazole, ivermectin, trimethoprim-sulfamethoxazole [TMP-SMX], furazolidone, nitazoxanide, secnidazole, fluconazole, nystatin, and itraconazole) at 10 different concentrationsin vitro. It was found that each subtype showed little sensitivity to the commonly used metronidazole, paromomycin, and triple therapy (furazolidone, nitazoxanide, and secnidazole). This study highlights the efficacy of other potential drug treatments, including trimethoprim-sulfamethoxazole and ivermectin, and suggests that current treatment regimens be revised.


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