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Assessment of the drug susceptibility of Plasmodium falciparum clinical isolates from africa by using a Plasmodium lactate dehydrogenase immunodetection assay and an inhibitory maximum effect model for precise measurement of the 50-percent inhibitory concentration.
Antimicrob Agents Chemother. 2006 Oct; 50(10):3343-9.AA

Abstract

The extension of drug resistance among malaria-causing Plasmodium falciparum parasites in Africa necessitates implementation of new combined therapeutic strategies. Drug susceptibility phenotyping requires precise measurements. Until recently, schizont maturation and isotopic in vitro assays were the only methods available, but their use was limited by technical constraints. This explains the revived interest in the development of replacement methods, such as the Plasmodium lactate dehydrogenase (pLDH) immunodetection assay. We evaluated a commercially controlled pLDH enzyme-linked immunosorbent assay (ELISA; the ELISA-Malaria antigen test; DiaMed AG, Cressier s/Morat, Switzerland) to assess drug susceptibility in a standard in vitro assay using fairly basic laboratory equipment to study the in vitro resistance of malaria parasites to major antimalarials. Five Plasmodium falciparum clones and 121 clinical African isolates collected during 2003 and 2004 were studied by the pLDH ELISA and the [8-(3)H]hypoxanthine isotopic assay as a reference with four antimalarials. Nonlinear regression with a maximum effect model was used to estimate the 50% inhibitory concentration (IC(50)) and its confidence intervals. The two methods were observed to have similar reproducibilities, but the pLDH ELISA demonstrated a higher sensitivity. The high correlation (r = 0.98) and the high phenotypic agreement (kappa = 0.88) between the two methods allowed comparison by determination of the IC(50)s. Recently collected Plasmodium falciparum African isolates were tested by pLDH ELISA and showed drug resistance or decreased susceptibilities of 62% to chloroquine and 11.5% to the active metabolite of amodiaquine. No decreased susceptibility to lumefantrine or the active metabolite of artemisinin was detected. The availability of this simple and highly sensitive pLDH immunodetection assay will provide an easier method for drug susceptibility testing of malaria parasites.

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Authors+Show Affiliations

Kaddouri H
Centre National de Référence du Paludisme, Laboratoire de Parasitologie, Hôpital Bichat-Claude Bernard and Université René Descartes, Paris, France.
Nakache S
No affiliation info available
Houzé S
No affiliation info available
Mentré F
No affiliation info available
Le Bras J
No affiliation info available

MeSH

AfricaAmodiaquineAnimalsAntimalarialsChloroquineDrug ResistanceEnzyme-Linked Immunosorbent AssayHumansInhibitory Concentration 50L-Lactate DehydrogenaseParasitic Sensitivity TestsPlasmodium falciparumReagent Kits, DiagnosticReproducibility of ResultsSensitivity and Specificity

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17005815

Citation

Kaddouri, Halima, et al. "Assessment of the Drug Susceptibility of Plasmodium Falciparum Clinical Isolates From Africa By Using a Plasmodium Lactate Dehydrogenase Immunodetection Assay and an Inhibitory Maximum Effect Model for Precise Measurement of the 50-percent Inhibitory Concentration." Antimicrobial Agents and Chemotherapy, vol. 50, no. 10, 2006, pp. 3343-9.
Kaddouri H, Nakache S, Houzé S, et al. Assessment of the drug susceptibility of Plasmodium falciparum clinical isolates from africa by using a Plasmodium lactate dehydrogenase immunodetection assay and an inhibitory maximum effect model for precise measurement of the 50-percent inhibitory concentration. Antimicrob Agents Chemother. 2006;50(10):3343-9.
Kaddouri, H., Nakache, S., Houzé, S., Mentré, F., & Le Bras, J. (2006). Assessment of the drug susceptibility of Plasmodium falciparum clinical isolates from africa by using a Plasmodium lactate dehydrogenase immunodetection assay and an inhibitory maximum effect model for precise measurement of the 50-percent inhibitory concentration. Antimicrobial Agents and Chemotherapy, 50(10), 3343-9.
Kaddouri H, et al. Assessment of the Drug Susceptibility of Plasmodium Falciparum Clinical Isolates From Africa By Using a Plasmodium Lactate Dehydrogenase Immunodetection Assay and an Inhibitory Maximum Effect Model for Precise Measurement of the 50-percent Inhibitory Concentration. Antimicrob Agents Chemother. 2006;50(10):3343-9. PubMed PMID: 17005815.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Assessment of the drug susceptibility of Plasmodium falciparum clinical isolates from africa by using a Plasmodium lactate dehydrogenase immunodetection assay and an inhibitory maximum effect model for precise measurement of the 50-percent inhibitory concentration. AU - Kaddouri,Halima, AU - Nakache,Serge, AU - Houzé,Sandrine, AU - Mentré,France, AU - Le Bras,Jacques, PY - 2006/9/29/pubmed PY - 2006/12/9/medline PY - 2006/9/29/entrez SP - 3343 EP - 9 JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 50 IS - 10 N2 - The extension of drug resistance among malaria-causing Plasmodium falciparum parasites in Africa necessitates implementation of new combined therapeutic strategies. Drug susceptibility phenotyping requires precise measurements. Until recently, schizont maturation and isotopic in vitro assays were the only methods available, but their use was limited by technical constraints. This explains the revived interest in the development of replacement methods, such as the Plasmodium lactate dehydrogenase (pLDH) immunodetection assay. We evaluated a commercially controlled pLDH enzyme-linked immunosorbent assay (ELISA; the ELISA-Malaria antigen test; DiaMed AG, Cressier s/Morat, Switzerland) to assess drug susceptibility in a standard in vitro assay using fairly basic laboratory equipment to study the in vitro resistance of malaria parasites to major antimalarials. Five Plasmodium falciparum clones and 121 clinical African isolates collected during 2003 and 2004 were studied by the pLDH ELISA and the [8-(3)H]hypoxanthine isotopic assay as a reference with four antimalarials. Nonlinear regression with a maximum effect model was used to estimate the 50% inhibitory concentration (IC(50)) and its confidence intervals. The two methods were observed to have similar reproducibilities, but the pLDH ELISA demonstrated a higher sensitivity. The high correlation (r = 0.98) and the high phenotypic agreement (kappa = 0.88) between the two methods allowed comparison by determination of the IC(50)s. Recently collected Plasmodium falciparum African isolates were tested by pLDH ELISA and showed drug resistance or decreased susceptibilities of 62% to chloroquine and 11.5% to the active metabolite of amodiaquine. No decreased susceptibility to lumefantrine or the active metabolite of artemisinin was detected. The availability of this simple and highly sensitive pLDH immunodetection assay will provide an easier method for drug susceptibility testing of malaria parasites. SN - 0066-4804 UR - https://www.unboundmedicine.com/medline/citation/17005815/Assessment_of_the_drug_susceptibility_of_Plasmodium_falciparum_clinical_isolates_from_africa_by_using_a_Plasmodium_lactate_dehydrogenase_immunodetection_assay_and_an_inhibitory_maximum_effect_model_for_precise_measurement_of_the_50_percent_inhibitory_concentration_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=17005815 DB - PRIME DP - Unbound Medicine ER -