<i>In vitro</i>sensitivity of<i>Plasmodium falciparum</i>to conventional and novel antimalarial drugs in Papua New Guinea

Wong, Rina P. M.; D, Lautu; Tavul, Livingstone; Hackett, S.; Siba, Peter; Karunajeewa, Harin; Ilett, Kenneth F.; Müeller, Ivo; Davis, Timothy M. E.

doi:10.1111/j.1365-3156.2009.02463.x

Cited by 22 publications

(33 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively, they can represent acquired resistance on the background of previous antimalarial resistance phenotypes. Previous studies of P. falciparum have documented positive correlations between the IC 50 s for the quinoline class of compounds and related drugs (38,40). The correlation of NQ with AQ, PIP, MFQ, and AS observed in P. falciparum isolates in the present study was similar to that reported from neighboring Papua New Guinea (38).…”

Section: Discussionsupporting

confidence: 80%

“…The IC 50 s of NQ in P. falciparum isolates (median IC 50 , 8.0 nM; interquartile range, 26.5 nM) were similar to those reported in culture-adapted P. falciparum isolates from Papua New Guinea (geometric mean, 7.0; 95% confidence interval [CI], 5.5 to 8.8 nM) (38). Our ex vivo study presents additional evidence for NQ's potent activities against highly CQ-resistant isolates of P. falciparum and P. vivax, revealing lower IC 50 s for NQ than for all of the standard drugs with the exception of AS.…”

Section: Discussionsupporting

confidence: 54%

See 1 more Smart Citation

Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax

Wirjanata

Sebayang

Chalfein

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

fThe 4-aminoquinoline naphthoquine (NQ) and the thiazine dye methylene blue (MB) have potent in vitro efficacies against Plasmodium falciparum, but susceptibility data for P. vivax are limited. The species-and stage-specific ex vivo activities of NQ and MB were assessed using a modified schizont maturation assay on clinical field isolates from Papua, Indonesia, where multidrugresistant P. falciparum and P. vivax are prevalent. Both compounds were highly active against P. falciparum . Stage-specific drug susceptibility assays revealed significantly greater IC 50 s in parasites exposed at the trophozoite stage than at the ring stage for NQ in P. falciparum (26.5 versus 5.1 nM, P ‫؍‬ 0.021) and P. vivax (341.6 versus 6.5 nM, P ‫؍‬ 0.021) and for MB in P. vivax (10.1 versus 1.6 nM, P ‫؍‬ 0.010). The excellent ex vivo activities of NQ and MB against both P. falciparum and P. vivax highlight their potential utility for the treatment of multidrug-resistant malaria in areas where both species are endemic.

show abstract

Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 54%

Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax

Wirjanata

Sebayang

Chalfein

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…This result reveals a pleiotropic role for this recently emerged pfcrt allele in modulating parasite susceptibility to clinically important antimalarials. This role differs from what is generally observed in Africa with the PfCRT CVIET haplotype or even the PfCRT SVMNT haplotype in Papua New Guinea (29,30). This effect of C350R on QN and MQ, however, was not replicated in field isolates, underscoring a complex genetic basis of susceptibility in the field.…”

Section: Discussioncontrasting

confidence: 46%

Adaptive evolution of malaria parasites in French Guiana: Reversal of chloroquine resistance by acquisition of a mutation in pfcrt

Moss

Dhingra

Volney

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

113

122

View full text Add to dashboard Cite

In regions with high malaria endemicity, the withdrawal of chloroquine (CQ) as first-line treatment of Plasmodium falciparum infections has typically led to the restoration of CQ susceptibility through the reexpansion of the wild-type (WT) allele K76 of the chloroquine resistance transporter gene (pfcrt) at the expense of less fit mutant alleles carrying the CQ resistance (CQR) marker K76T. In low-transmission settings, such as South America, drug resistance mutations can attain 100% prevalence, thereby precluding the return of WT parasites after the complete removal of drug pressure. In French Guiana, despite the fixation of the K76T allele, the prevalence of CQR isolates progressively dropped from >90% to <30% during 17 y after CQ withdrawal in 1995. Using a genome-wide association study with CQ-sensitive (CQS) and CQR isolates, we have identified a single mutation in pfcrt encoding a C350R substitution that is associated with the restoration of CQ susceptibility. Genome editing of the CQR reference strain 7G8 to incorporate PfCRT C350R caused a complete loss of CQR. A retrospective molecular survey on 580 isolates collected from 1997 to 2012 identified all C350R mutant parasites as being CQS. This mutation emerged in 2002 and rapidly spread throughout the P. falciparum population. The C350R allele is also associated with a significant decrease in piperaquine susceptibility in vitro, suggesting that piperaquine pressure in addition to potential fitness costs associated with the 7G8-type CQR pfcrt allele may have selected for this mutation. These findings have important implications for understanding the evolutionary dynamics of antimalarial drug resistance. malaria | drug resistance | evolution | Plasmodium falciparum | PfCRT

show abstract

“…It is suspected that cross-resistance might occur between PPQ and other quinoline drugs because of structural similarities of these drugs and possibly shared modes of ac- tion (46). Studies showing correlation between in vitro susceptibilities of parasite isolates to CQ and PPQ (20,22,24,25,32) and demonstration of elevated resistance to PPQ in well-characterized laboratory CQ-resistant parasite lines (25,26) suggest a role of the major CQ-resistant marker pfcrt in PPQ resistance. However, it is noteworthy that the difference between the PPQ responses in CQsensitive and -resistant strains which led to the suggestion of cross-resistance between CQ and PPQ resistance was insignificant and only at 3-to 4-fold (Table 2).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Sensitivities of Plasmodium falciparum Isolates from the China-Myanmar Border to Piperaquine and Association with Polymorphisms in Candidate Genes

Hao

Jia²,

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

eThe recent reports of resistance in Plasmodium falciparum to artemisinin derivatives and their partner drugs demand intensive studies toward understanding the molecular mechanisms of resistance. In this study, we examined the in vitro susceptibility of 63 P. falciparum field isolates collected from the China-Myanmar border area to chloroquine (CQ) and piperaquine (PPQ). Parasite isolates remained highly resistant to CQ, with the geometric mean 50% inhibitory concentration (IC 50 ) of 252.7 nM and a range of 51.9 to 1,052.0 nM. In comparison, these parasites had a geometric mean IC 50 of 28.4 nM for PPQ, with a fairly wide range of 5.3 to 132.0 nM, suggesting that certain parasite isolates displayed relatively high levels of resistance to PPQ. Interestingly, within the 4 years of study, the parasites exhibited a continuous decline in susceptibilities to both CQ and PPQ, and there was a significant correlation between responses to CQ and PPQ (Pearson correlation coefficient ‫؍‬ 0.79, P < 0.0001). Consistent with the CQ-resistant phenotype, all parasites carried the pfcrt K76T mutation, and most parasites had the CVIET type that is prevalent in Southeast Asia. In contrast, pfmdr1 mutations were relatively rare, and no gene amplification was detected. Only the pfmdr1 N1042D mutation was associated with resistance to CQ. For the pfmrp1 gene, four substitutions reached relatively high prevalence of >22%, and the I876V mutation was associated with reduced sensitivity to CQ. However, we could not establish a link between PPQ responses and the polymorphisms in the three genes associated with quinoline drug resistance.

show abstract

In vitrosensitivity ofPlasmodium falciparumto conventional and novel antimalarial drugs in Papua New Guinea

Cited by 22 publications

References 50 publications

Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax

Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax

Adaptive evolution of malaria parasites in French Guiana: Reversal of chloroquine resistance by acquisition of a mutation in pfcrt

In Vitro Sensitivities of Plasmodium falciparum Isolates from the China-Myanmar Border to Piperaquine and Association with Polymorphisms in Candidate Genes

Contact Info

Product

Resources

About