scholarly journals An Allosteric Inhibitory Potential of Triterpenes from Combretum racemosum on the Structural and Functional Dynamics of Plasmodium falciparum Lactate Dehydrogenase Binding Landscape

Author(s):  
Wande M. Oluyemi ◽  
Babatunde B. Samuel ◽  
Adeniyi T. Adewumi ◽  
Yemi A. Adekunle ◽  
Mahmoud E. S. Soliman ◽  
...  
2006 ◽  
Vol 50 (10) ◽  
pp. 3343-3349 ◽  
Author(s):  
Halima Kaddouri ◽  
Serge Nakache ◽  
Sandrine Houzé ◽  
France Mentré ◽  
Jacques Le Bras

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 [8-3H]hypoxanthine isotopic assay as a reference with four antimalarials. Nonlinear regression with a maximum effect model was used to estimate the 50% inhibitory concentration (IC50) 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 (κ = 0.88) between the two methods allowed comparison by determination of the IC50s. 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.


2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Eva A. Nambati ◽  
William C. Kiarie ◽  
Francis Kimani ◽  
James H. Kimotho ◽  
Maureen S. Otinga ◽  
...  

Author(s):  
Colleen M. Leonard ◽  
Hussein Mohammed ◽  
Mekonnen Tadesse ◽  
Jessica N. McCaffery ◽  
Doug Nace ◽  
...  

Plasmodium falciparum and Plasmodium vivax are co-endemic in Ethiopia. This study investigated whether mixed infections were missed by microscopy from a 2017 therapeutic efficacy study at two health facilities in Ethiopia. All patients (N = 304) were initially classified as having single-species P. falciparum (n = 148 samples) or P. vivax infections (n = 156). Dried blood spots were tested for Plasmodium antigens by bead-based multiplex assay for pan-Plasmodium aldolase, pan-Plasmodium lactate dehydrogenase, P. vivax lactate dehydrogenase, and histidine-rich protein 2. Of 304 blood samples, 13 (4.3%) contained both P. falciparum and P. vivax antigens and were analyzed by polymerase chain reaction for species-specific DNA. Of these 13 samples, five were confirmed by polymerase chain reaction for P. falciparum/P. vivax co-infection. One sample, initially classified as P. vivax by microscopy, was found to only have Plasmodium ovale DNA. Plasmodium falciparum/P. vivax mixed infections can be missed by microscopy even in the context of a therapeutic efficacy study with multiple trained readers.


FEBS Journal ◽  
2007 ◽  
Vol 274 (11) ◽  
pp. 2738-2748 ◽  
Author(s):  
Deborah K. Shoemark ◽  
Matthew J. Cliff ◽  
Richard B. Sessions ◽  
Anthony R. Clarke

Author(s):  
Shiraz Gefen-Halevi ◽  
Valentin Belinson ◽  
Uri Manor ◽  
Zeala Gazit ◽  
Gill Smollan ◽  
...  

A 65-year-old Israeli working in Welkait, Ethiopia, not using malaria prophylaxis, developed fever. Malaria rapid detection test was consistent with non-falciparum malaria (plasmodium lactate dehydrogenase+/histidine-rich protein− [LDH+/HRP−]) but microscopy showed typical Plasmodium falciparum. HRP2/3 were negative by polymerase chain reaction. The patient suffered two recrudescence episodes following artemether–lumefantrine and atovaquone–proguanil treatments, and responded to mefloquine treatment.


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