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
Language: 
English
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.

Author(s): 
Kaddouri, Halima
Nakache, Serge
Houzé, Sandrine
Mentré, France
Le Bras, Jacques
Item Type: 
Journal Article
Publication Title: 
Antimicrobial Agents and Chemotherapy
Journal Abbreviation: 
Antimicrob. Agents Chemother.
Publication Date: 
10/6/2015
Publication Year: 
2006
Pages: 
3343-3349
Volume: 
50
Issue: 
10
ISSN: 
0066-4804
DOI: 
10.1128/AAC.00367-06
Library Catalog: 
PubMed
Extra: 
PMID: 17005815 PMCID: PMC1610081

Turabian/Chicago Citation

Halima Kaddouri, Serge Nakache, Sandrine Houzé, France Mentré and Jacques Le Bras. 10/6/2015. "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: 3343-3349. 10.1128/AAC.00367-06.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1128/AAC.00367-06 | issn = 0066-4804 | volume = 50 | pages = 3343-3349 | last = Kaddouri | first = Halima | coauthors = Nakache, Serge, Houzé, Sandrine, Mentré, France, Le Bras, Jacques | title = 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 | journal = Antimicrobial Agents and Chemotherapy | date = 10/6/2015 | pmid = | pmc = }} </ref>