Inverse correlation of sensitivity in vitro of Plasmodium falciparum to chloroquine and mefloquine in Ghana

Wernsdorfer, Walther H.; Landgraf, Barbara; Wiedermann, G; Kollaritsch, Herwig

doi:10.1016/0035-9203(94)90426-x

Cited by 13 publications

(6 citation statements)

References 5 publications

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“…This is also consistent with the acceptable clinical efficacy of artesunate–amodiaquine in some [59, 60], but not all [61], parts of SEA within the last decade. Furthermore, the inverse correlation between susceptibility to 4-aminoquinolines and mefloquine [62, 63] offers the potential to combine two partners with opposing resistance mechanisms within a novel ‘triple’ ACT, artemether–lumefantrine plus amodiaquine [64]; this is currently under investigation in the follow-up study to TRAC (ClinicalTrials.gov NCT02453308).…”

Section: Discussionmentioning

confidence: 99%

Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration

Srimuang

Miotto

Lim

et al. 2016

Malar J

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BackgroundDeclining anti-malarial efficacy of artemisinin-based combination therapy, and reduced Plasmodium falciparum susceptibility to individual anti-malarials are being documented across an expanding area of Southeast Asia (SEA). Genotypic markers complement phenotypic studies in assessing the efficacy of individual anti-malarials.MethodsThe markers pfmdr1 and pfcrt were genotyped in parasite samples obtained in 2011–2014 at 14 TRAC (Tracking Resistance to Artemisinin Collaboration) sites in mainland Southeast Asia using a combination of PCR and next-generation sequencing methods.Results Pfmdr1 amplification, a marker of mefloquine and lumefantrine resistance, was highly prevalent at Mae Sot on the Thailand–Myanmar border (59.8% of isolates) and common (more than 10%) at sites in central Myanmar, eastern Thailand and western Cambodia; however, its prevalence was lower than previously documented in Pailin, western Cambodia. The pfmdr1 Y184F mutation was common, particularly in and around Cambodia, and the F1226Y mutation was found in about half of samples in Mae Sot. The functional significance of these two mutations remains unclear. Other previously documented pfmdr1 mutations were absent or very rare in the region. The pfcrt mutation K76T associated with chloroquine resistance was found in 98.2% of isolates. The CVIET haplotype made up 95% or more of isolates in western SEA while the CVIDT haplotype was common (30–40% of isolates) in north and northeastern Cambodia, southern Laos, and southern Vietnam.ConclusionsThese findings generate cause for concern regarding the mid-term efficacy of artemether–lumefantrine in Myanmar, while the absence of resistance-conferring pfmdr1 mutations and SVMNT pfcrt haplotypes suggests that amodiaquine could be an efficacious component of anti-malarial regimens in SEA.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1598-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration

Srimuang

Miotto

Lim

et al. 2016

Malar J

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“…First, as previously suggested, 14 there may be a lack of predictive value of performance in vivo by in vitro data. Second, there may be a play of the inverse relationship in sensitivity in vitro in isolates of P. falciparum to MQ and CQ, 14,29 because CQ resistance is currently high grade in the area. 30 Third, until recently, the very limited use of MQ in the area since the early 1990s may have allowed restoration of sensitivity to isolates with reduced sensitivity in vitro .…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Efficacy and Effects of Artesunate-Mefloquine and Mefloquine Alone on Malaria-Associated Anemia in Children with Uncomplicated Plasmodium falciparum Malaria in Southwest Nigeria

Sowunmi

Gbotosho

Happi

et al. 2009

The American Journal of Tropical Medicine and Hygiene

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Abstract. The treatment efficacy and effects of artesunate-mefloquine (AMQ) and mefloquine (MQ) on malariaassociated anemia (MAA) were evaluated in 342 children ≤ 10 years of age with uncomplicated Plasmodium falciparum malaria randomized to receive either drug/drug combination. All children recovered clinically. Fever clearance times were similar. Parasite clearance was significantly faster with AMQ (mean ± SD = 1.4 ± 0.6 days, 95% confidence interval [CI] = 1.3-1.5, P < 0.0001), but polymerase chain reaction-corrected cure rates were similar (97% versus 94%). Gametocyte carriage rates and the drug-attributable fall in hematocrit were significantly lower with AMQ (mean ± SD = 4.8 ± 3.8%, 95% CI = 3.6-6.0, P = 0.03), but the rates of resolution of MAA were similar. Both regimens were well tolerated. AMQ clears parasitemia and reduces gametocyte carriage more rapidly and causes lesser fall in hematocrit than MQ, but both regimens are effective treatment of uncomplicated P. falciparum malaria in Nigerian children.

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“…This is consistent with reports of a genetically determined cross-resistance between mefloquine, halofantrine, and quinine 27 and an inverse correlation between chloroquine and mefloquine. 28 Resistance to mefloquine and susceptibility to chloroquine was reported to be linked to the P. falciparum multiple drug resistance (mdr)1 gene. 29 A positive correlation between the in vitro responses to mefloquine, halofantrine, and quinine was observed in the Lambarene area in 1992.…”

Section: Discussionmentioning

confidence: 99%

Follow-up of the susceptibility of Plasmodium falciparum to antimalarials in Gabon.

Philipps

Radloff²,

Wernsdorfer³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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The sensitivity of Plasmodium falciparum to chloroquine, mefloquine, quinine, quinidine, halofantrine, artemisinin, and sulfadoxine/pyrimethamine was investigated in Lambarene, Gabon in 1994. The development of in vitro susceptibility has been traced from 1983 or 1992 to 1994 for chloroquine, mefloquine, halofantrine, and quinine. Standard in vitro microtests according to World Health Organization methodology were performed. Of 33 isolates tested for susceptibility to chloroquine, 31 were resistant, one was borderline, and one isolate was sensitive (mean 50% effective concentration [EC 50 ] ϭ 1.38 mol/L of blood). With mefloquine, all isolates were fully inhibited below the threshold of resistance (mean EC 50 ϭ 0.51 mol/L of blood). Of 32 isolates tested with quinine, six had borderline resistance (mean EC 50 ϭ 0.54 mol/L of blood medium mixture). Susceptibility to quinidine was higher with a mean EC 50 of 0.15 mol/L of blood medium mixture. With halofantrine, 26 of 32 isolates matured at 3 nmol/L of blood medium mixture (mean EC 50 ϭ 1.64 nmol/L of blood medium mixture), indicating a steep decrease in susceptibility in comparison with 1992. For artemisinin, the mean EC 50 was 97.92 nmol/L of blood medium mixture. Sulfadoxine/ pyrimethamine showed five of 16 resistant isolates with a mean EC 50 of 2.46 nmol/L of blood medium mixture. Whereas chloroquine resistance remained stable with a tendency to decrease, susceptibility to mefloquine and quinine was slightly decreased. A significant increase in the mean EC 50 and EC 90 in comparison with our previous data from Gabon was found for halofantrine.

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Inverse correlation of sensitivity in vitro of Plasmodium falciparum to chloroquine and mefloquine in Ghana

Cited by 13 publications

References 5 publications

Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration

Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration

Therapeutic Efficacy and Effects of Artesunate-Mefloquine and Mefloquine Alone on Malaria-Associated Anemia in Children with Uncomplicated Plasmodium falciparum Malaria in Southwest Nigeria

Follow-up of the susceptibility of Plasmodium falciparum to antimalarials in Gabon.

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