Method for Evaluation of Drug Resistance for Plasmodium Falciparum. Phase 2

1991 ◽  
Author(s):  
Michael T. Makler
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Phase 2

scholarly journals 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

2006 ◽  
Vol 50 (10) ◽  
pp. 3343-3349 ◽  
Author(s):  
Halima Kaddouri ◽  
Serge Nakache ◽  
Sandrine Houzé ◽  
France Mentré ◽  
Jacques Le Bras
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Lactate Dehydrogenase ◽  
Active Metabolite ◽  
Inhibitory Concentration ◽  
Drug Susceptibility ◽  
Maximum Effect ◽  
Malaria Parasites ◽  
Effect Model

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.

Detection of Genetic markers associated with Plasmodium falciparum drug resistance among malaria patients in Kaduna State, Nigeria

2021 ◽  
Vol 42 (2) ◽  
pp. 206-213
Author(s):  
G.Y. Benjamin ◽  
H.I. Inabo ◽  
M.H.I. Doko ◽  
B.O. Olayinka
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Phylogenetic Tree ◽  
Genetic Markers ◽  
Cross Sectional Study ◽  
Sub Saharan Africa ◽  
Health Concern ◽  
Cross Sectional ◽  
Blood Samples ◽  
Test Kit

Malaria is a disease of public health concern in Nigeria and sub-Saharan Africa. It is caused by intracellular parasites of the genus Plasmodium. The aim of this study was to detect genetic markers associated with Plasmodium falciparum drug resistance among malaria patients in Kaduna State, Nigeria. The study was a cross-sectional study that lasted from May 2018 to October 2018. Three hundred blood samples were collected from consenting individuals attending selected hospitals, in the three senatorial districts of Kaduna State, Nigeria. Structured questionnaire were used to obtain relevant data from study participants. The blood samples were screened for malaria parasites using microscopy and rapid diagnostic test kit. Polymerase Chain Reaction was used for detection of the drug resistance genes. Pfcrt, pfmdr1, pfdhfr, pfdhps and pfatpase6 genes were detected at expected amplicon sizes from the malaria positive samples. The pfatpase6 PCR amplicons were sequenced and a phylogenetic tree was created to determine their relatedness. Result showed that Pfcrt (80%) had the highest prevalence, followed by pfdhfr (60%), pfmdr1 (36%) and pfdhps (8%). Pfatpase6 was also detected in 73.3% of the samples, and a phylogenetic tree showed relatedness between the pfatpase6  sequences in this study and those deposited in the GenBank. In conclusion, the study detected that Plasmodium falciparum genes were associated with drug resistance to commonly used antimalarials.

History and current status of Plasmodium falciparum antimalarial drug resistance in Madagascar

2010 ◽  
Vol 42 (1) ◽  
pp. 22-32 ◽  
Author(s):  
Valérie Andriantsoanirina ◽  
Didier Ménard ◽  
Luciano Tuseo ◽  
Rémy Durand
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Antimalarial Drug ◽  
Current Status ◽  
Antimalarial Drug Resistance

scholarly journals Piperaquine resistant Cambodian Plasmodium falciparum clinical isolates: in vitro genotypic and phenotypic characterization

2020 ◽  
Author(s):  
Nonlawat Boonyalai ◽  
Brian A Vesely ◽  
Chatchadaporn Thamnurak ◽  
Chantida Praditpol ◽  
Watcharintorn Fagnark ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Copy Number ◽  
Drug Susceptibility ◽  
Antagonistic Activity ◽  
Drug Combinations ◽  
Chloroquine Resistance ◽  
Phenotypic Characterization ◽  
Field Isolates

Abstract Background High rates of dihydroartemisinin-piperaquine (DHA-PPQ) treatment failures have been documented for uncomplicated Plasmodium falciparum in Cambodia. The genetic markers plasmepsin 2 ( pfpm2 ), exonuclease ( pfexo ) and chloroquine resistance transporter ( pfcrt ) genes are associated with PPQ resistance and are used for monitoring the prevalence of drug resistance and guiding malaria drug treatment policy.Methods To examine the relative contribution of each marker to PPQ resistance, in vitro culture and the PPQ survival assay were performed on seventeen P. falciparum isolates from northern Cambodia, and the presence of E415G-Exo and pfcrt mutations (T93S, H97Y, F145I, I218F, M343L, C350R, and G353V) as well as pfpm2 copy number polymorphisms were determined. Parasites were then cloned by limiting dilution and the cloned parasites were tested for drug susceptibility. Isobolographic analysis of several drug combinations for standard clones and newly cloned P. falciparum Cambodian isolates was also determined.Results The characterization of culture-adapted isolates revealed that the presence of novel pfcrt mutations (T93S, H97Y, F145I, and I218F) with E415G-Exo mutation can confer PPQ-resistance, in the absence of pfpm2 amplification. In vitro testing of PPQ resistant parasites demonstrated a bimodal dose-response, the existence of a swollen digestive vacuole phenotype, and an increased susceptibility to quinine, chloroquine, mefloquine and lumefantrine. To further characterize drug sensitivity, parental parasites were cloned in which a clonal line, 14-B5, was identified as sensitive to artemisinin and piperaquine, but resistant to chloroquine. Assessment of the clone against a panel of drug combinations revealed antagonistic activity for six different drug combinations. However, mefloquine-proguanil and atovoquone-proguanil combinations revealed synergistic antimalarial activity.Conclusions Surveillance for PPQ resistance in regions relying on DHA-PPQ as the first-line treatment is dependent on the monitoring of molecular markers of drug resistance. P. falciparum harbouring novel pfcrt mutations with E415G-exo mutations displayed PPQ resistant phenotype. The presence of pfpm2 amplification was not required to render parasites PPQ resistant suggesting that the increase in pfpm2 copy number alone is not the sole modulator of PPQ resistance. Genetic background of circulating field isolates appear to play a role in drug susceptibility and biological responses induced by drug combinations. The use of latest field isolates may be necessary for assessment of relevant drug combinations against P. falciparum strains and when down-selecting novel drug candidates.

scholarly journals Molecular Surveillance of Plasmodium falciparum Drug Resistance Markers in Clinical Samples from Botswana

2018 ◽  
Vol 99 (6) ◽  
pp. 1499-1503 ◽  
Author(s):  
Leabaneng Tawe ◽  
Michela Menegon ◽  
Pleasure Ramatlho ◽  
Charles W. Muthoga ◽  
Naledi Mutukwa ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Clinical Samples ◽  
Molecular Surveillance ◽  
Resistance Markers

scholarly journals ISOLATION AND PRESENCE OF ANTIMALARIAL ACTIVITIES OF MARINE SPONGE Xestospongia sp.

2013 ◽  
Vol 13 (3) ◽  
pp. 199-204 ◽  
Author(s):  
Murtihapsari Murtihapsari ◽  
Apriani Sulu Parubak ◽  
Bertha Mangallo ◽  
Wiwied Ekasari ◽  
Puji Budi Asih ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Secondary Metabolites ◽  
Marine Sponge ◽  
Spectrum Analysis ◽  
Extraction Method ◽  
Rapid Evolution ◽  
Hexane Extraction ◽  
Marine Life ◽  
Plausible Structure

Plasmodium falciparum, the agent of malignant malaria, is one of mankind's most severe scourges, mainly in the tropic world. Efforts to develop preventive vaccines or remedial drugs are handicapped by the parasite's rapid evolution of drug resistance. Here, we presented an advance work on examination of antimalarial component from marine life of Xestospongia sp., the study is based on hexane extraction method. The premier result, we obtained five fractions. Among these five fractions, the fourth has the most potent inhibitory against the growth of P. falciparum 3D7 with an IC50: 7.13 µg/mL. A compiled spectrum analysis, FTIR, 1H-NMR and GC-MS, revealed that the fourth fraction consisted abundantly of two secondary metabolites such as flavonoids and triterpenoids. Finally, our results suggest a plausible structure rooted to the base of ibuprofen.

scholarly journals Artemisinin-independent inhibitory activity of Artemisia sp. infusions against different Plasmodium stages including relapse-causing hypnozoites

2021 ◽  
Vol 5 (3) ◽  
pp. e202101237
Author(s):  
Kutub Ashraf ◽  
Shahin Tajeri ◽  
Christophe-Sébastien Arnold ◽  
Nadia Amanzougaghene ◽  
Jean-François Franetich ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Inhibitory Activity ◽  
Parasite Species ◽  
Artemisia Annua ◽  
Combination Therapies ◽  
Lead Compounds ◽  
Low Concentrations ◽  
Inhibitory Activities

Artemisinin-based combination therapies (ACT) are the frontline treatments against malaria worldwide. Recently the use of traditional infusions from Artemisia annua (from which artemisinin is obtained) or Artemisia afra (lacking artemisinin) has been controversially advocated. Such unregulated plant-based remedies are strongly discouraged as they might constitute sub-optimal therapies and promote drug resistance. Here, we conducted the first comparative study of the anti-malarial effects of both plant infusions in vitro against the asexual erythrocytic stages of Plasmodium falciparum and the pre-erythrocytic (i.e., liver) stages of various Plasmodium species. Low concentrations of either infusion accounted for significant inhibitory activities across every parasite species and stage studied. We show that these antiplasmodial effects were essentially artemisinin-independent and were additionally monitored by observations of the parasite apicoplast and mitochondrion. In particular, the infusions significantly incapacitated sporozoites, and for Plasmodium vivax and P. cynomolgi, disrupted the hypnozoites. This provides the first indication that compounds other than 8-aminoquinolines could be effective antimalarials against relapsing parasites. These observations advocate for further screening to uncover urgently needed novel antimalarial lead compounds.

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