Medikamentensensibilität von Plasmodium falciparum entlang der thailändischen Grenze bestimmt mittels des neuen HRP2-in-vitro-Feldtests

Attlmayr, Bernhard; Kollaritsch, Herwig; Wernsdorfer, Walther H.; Miller, R. Scott; Sirichaisinthop, Jeeraphat; Noedl, Harald

doi:10.1007/s00508-005-0445-5

Cited by 4 publications

(5 citation statements)

References 16 publications

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“…2008). There were generally weak associations between DHA IC 50 s and those of other drugs, consistent with the findings of others (Basco & Ringwald 2003; Attlmayr et al. 2005; Pradines et al.…”

Section: Discussionsupporting

confidence: 91%

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

Wong

Tavul

et al. 2010

Tropical Medicine &Amp; International Health

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Summaryobjective Recent clinical studies have shown high rates of malaria treatment failure in endemic areas of Papua New Guinea (PNG), necessitating a change of treatment from chloroquine (CQ) or amodiaquine (AQ) plus sulphadoxine-pyrimethamine to the artemisinin combination therapy (ACT) artemether plus lumefantrine (LM). To facilitate the monitoring of antimalarial drug resistance in this setting, we assessed the in vitro sensitivity of Plasmodium falciparum isolates from Madang Province.methods A validated colorimetric lactate dehydrogenase assay was used to assess growth inhibition of 64 P. falciparum isolates in the presence of nine conventional or novel antimalarial drugs [CQ, AQ, monodesethyl-amodiaquine (DAQ), piperaquine (PQ), naphthoquine (NQ), mefloquine (MQ), LM, dihydroartemisinin and azithromycin (AZ)].results The geometric mean (95% confidence interval) concentration required to inhibit parasite growth by 50% (IC 50 ) was 167 (141-197) nm for CQ, and 82% of strains were resistant (threshold 100 nm), consistent with near-fixation of the CQ resistance-associated pfcrt allele in PNG. Except for AZ [8.351 (5.418-12.871) nm], the geometric mean IC 50 for the other drugs was <20 nm. There were strong associations between the IC 50 s of 4-aminoquinoline (CQ, AQ, DAQ and NQ), bisquinoline (PQ) and aryl aminoalcohol (MQ) compounds suggesting cross-resistance, but LM IC 50 only correlated with that of MQ.conclusions Most PNG isolates are resistant to CQ in vitro but not to other ACT partner drugs. The non-isotopic semi-automated high-throughput nature of the Plasmodium lactate dehydrogenase assay facilitates the convenient serial assessment of local parasite sensitivity, so that emerging resistance can be identified with relative confidence at an early stage.

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Section: Discussionsupporting

confidence: 91%

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

Wong

Tavul

et al. 2010

Tropical Medicine &Amp; International Health

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“…There was even one isolate that was sensitive to CQ. In 1991–1992 and 1994, the degree of CQ resistance in the country was high [median (95% CI) IC 50 193.2 (148.24-251.85) and 157.0 (124.11-198.73) nM, respectively] [27], but was improved during the 1997, 1999 and 2004–2009 [median (95% CI) IC 50 : 157.0 (128.0–193.0), 120.5 (105.7–137.3) and 70.0 (10.0-183.0) nM, respectively] [18,36,37]. Molecular analysis in either laboratory or field P. falciparum isolates demonstrated the strong linkage between CQ resistance and pfcrt gene mutations [20,22,38].…”

Section: Discussionmentioning

confidence: 99%

“…Susceptibility of the parasite to CQ was also shown in this study to link with pfmrp1 polymorphism, of which the 191Y mutation resulted in increased susceptibility of the parasite to CQ. For QN, a decline in parasite sensitivity to the drug was obviously observed during 1991–1992 and 1994 [mean (95% CI) IC 50 576.2 (460.51-720.99) and 403.9 (330.50-493.54) nM, respectively], but was improved during 1997–2008 [18,36,37,39]. A total of 16 isolates were identified as QN resistance, 12 and four isolates collected during 2006–2007 and 2008–2009, respectively.…”

Section: Discussionmentioning

confidence: 99%

Four years’ monitoring of in vitro sensitivity and candidate molecular markers of resistance of Plasmodium falciparum to artesunate-mefloquine combination in the Thai-Myanmar border

Phompradit

Muhamad

Wisedpanichkij

et al. 2014

Malar J

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BackgroundThe decline in efficacy of artesunate (AS) and mefloquine (MQ) is now the major concern in areas along the Thai-Cambodian and Thai-Myanmar borders.MethodsThe correlation between polymorphisms of pfatp6, pfcrt, pfmdr1 and pfmrp1 genes and in vitro sensitivity of Plasmodium falciparum isolates to the artemisinin-based combination therapy (ACT) components AS and MQ, including the previously used first-line anti-malarial drugs chloroquine (CQ) and quinine (QN) were investigated in a total of 119 P. falciparum isolates collected from patients with uncomplicated P. falciparum infection during 2006–2009.ResultsReduced in vitro parasite sensitivity to AS [median (95% CI) IC50 3.4 (3.1-3.7) nM] was found in 42% of the isolates, whereas resistance to MQ [median (95% CI) IC50 54.1 (46.8-61.4) nM] accounted for 58% of the isolates. Amplification of pfmdr1 gene was strongly associated with a decline in susceptibility of P. falciparum isolates to AS, MQ and QN. Significant difference in IC50 values of AS, MQ and QN was observed among isolates carrying one, two, three, and ≥ four gene copies [median (95% CI) AS IC50: 1.6 (1.3-1.9), 1.8 (1.1-2.5), 2.9 (2.1-3.7) and 3.1 (2.5-3.7) nM, respectively; MQ IC50: 19.2 (15.8-22.6), 37.8 (10.7-64.8), 55.3 (47.7-62.9) and 63.6 (49.2-78.0) nM, respectively; and QN IC50: 183.0 (139.9-226.4), 256.4 (83.7-249.1), 329.5 (206.6-425.5) and 420.0 (475.2-475.6) nM, respectively]. The prevalence of isolates which were resistant to QN was reduced from 21.4% during the period 2006–2007 to 6.3% during the period 2008–2009. Pfmdr1 86Y was found to be associated with increased susceptibility of the parasite to MQ and QN. Pfmdr1 1034C was associated with decreased susceptibility to QN. Pfmrp1 191Y and 1390I were associated with increased susceptibility to CQ and QN, respectively.ConclusionHigh prevalence of CQ and MQ-resistant P. falciparum isolates was observed during the four-year observation period (2006–2009). AS sensitivity was declined, while QN sensitivity was improved. Pfmdr1 and pfmrp1 appear to be the key genes that modulate multidrug resistance in P. falciparum.

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“…These diagnostic strips are based on antigens expressed by the parasite during the erythrocyte stage such as histidine-rich protein-2 (HRP2) [8-10] or lactate dehydrogenase (LDH) [11]. HRP2 is involved in haemozoin formation, while [12] Plasmodium falciparum LDH catalyzes the conversion of lactate into pyruvate and nicotinamide adenine dinucleotide (NADH) [13], a reaction essential to parasite survival.…”

Section: Introductionmentioning

confidence: 99%

Use of a pLDH-based dipstick in the diagnostic and therapeutic follow-up of malaria patients in Mali

Ouattara

Doumbo

Saye

et al. 2011

Malar J

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BackgroundMalaria is a major public health problem in Mali and diagnosis is typically based on microscopy. Microscopy requires a well trained technician, a reliable power source, a functioning microscope and adequate supplies. The scarcity of resources of community health centres (CHC) does not allow for such a significant investment in only one aspect of malaria control. In this context, Rapid Diagnostic Tests (RDTs) may improve case management particularly in remote areas.MethodsThis multicentre study included 725 patients simultaneously screened with OptiMal-IT test and thick smears for malaria parasite detection. While evaluating the therapeutic efficacy of choroquine in 2 study sites, we compared the diagnostic values of thick smear microscopy to OptiMal-IT test applying the WHO 14 days follow-up scheme using samples collected from 344 patients.ResultsThe sensitivity and the specificity of OptiMal-IT compared to thick smear was 97.2% and 95.4%, whereas the positive and negative predictive values were 96.7 and 96.1%, respectively. The percent agreement between the two diagnostic tests was 0.93. The two tests were comparable in detecting malaria at day 0, day 3 and day 14. The only difference was observed at day 7 due to high gametocytemia. Subjectively, health care providers found OptiMal-IT easier to use and store under field conditions.ConclusionOptiMal-IT test revealed similar results when compared to microscopy which is considered the gold standard for malaria diagnostics. The test was found to have a short processing time and was easier to use. These advantages may improve malaria case management by providing a diagnostic and drug efficacy follow-up tool to peripheral health centres with limited resources.

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Medikamentensensibilität von Plasmodium falciparum entlang der thailändischen Grenze bestimmt mittels des neuen HRP2-in-vitro-Feldtests

Cited by 4 publications

References 16 publications

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

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

Four years’ monitoring of in vitro sensitivity and candidate molecular markers of resistance of Plasmodium falciparum to artesunate-mefloquine combination in the Thai-Myanmar border

Use of a pLDH-based dipstick in the diagnostic and therapeutic follow-up of malaria patients in Mali

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