scholarly journals Phenylurenyl Benzamide Analogues as a New Antimalarial Chemotype that Potently Kill Chloroquine Resistant Parasite

2016 ◽  
Vol 82 (1) ◽  
Author(s):  
K. C. Ravindra ◽  
Dhaneshwar Prusty ◽  
B Ruthrotha Selvi ◽  
Deepthi Sudarshan ◽  
Suman K. Dhar ◽  
...  
Keyword(s):  
Resistant Parasite

scholarly journals Status of anthelmintic resistance of gastrointestinal nematodes in organized sheep and goat farms

2018 ◽  
Vol 4 (4) ◽  
pp. 378-382 ◽  
Author(s):  
Saiful Islam ◽  
Anita Rani Dey ◽  
Shirin Akter ◽  
Hiranmoy Biswas ◽  
Md Hasanuzzaman Talukder ◽  
...  
Keyword(s):  
Lower Limit ◽  
Anthelmintic Resistance ◽  
Small Ruminants ◽  
Gastrointestinal Nematodes ◽  
Fecal Samples ◽  
Resistant Parasite ◽  
Fecal Egg Count ◽  
Sheep Farm ◽  
Before And After ◽  
The Status

Anthelmintic resistance has become a global problem that threatens livestock production worldwide. The present study was investigated the status of anthelmintic resistance in gastrointestinal (GI) nematodes of small ruminants in two organized sheep and goat farms in two different areas of Bangladesh by fecal egg count reduction test (FECRT) for albendazole, levamisole and ivermectin. In each farms, naturally infected animals were divided into four groups of 10 animals. Fecal samples from each group were collected on day 0 and day 14 of post treatment to measure the eggs per gram of feces (EPG). The fecal samples of each group before and after treatment were also considered for culture to identify resistant parasite. In case of organized sheep farm, the result of FECRT of albendazole was 90.17, 95% confidence with upper and lower limit was 97.82 and 55.68, respectively. The result of FECRT of levamisole and ivermectin was 98.25 and 96.77, 95% confidence with upper and lower limit was 99.79, 85.12 and 99.11, 88.31, respectively. In case of organized goat farm, the result of FECRT of albendazole was 100, 95% confidence with upper and lower limit was 0 and 0, respectively. The result of FECRT of levamisole and ivermectin was 97.99 and 100, 95% confidence with upper and lower limit was 99.59, 90.28 and 0, 0 respectively. The results revealed that gastrointestinal nematodes were found to be resistant to albendazole in organized sheep farm and suspected to be resistant to levamisole and ivermectin. In organized goat farms, the GI nematodes found to be susceptible to all anthelmintics used for this study. Coproculture revealed that Haemonchus spp. were resistant parasite in sheep farm. This seems to be the first documentation of anthelmintic resistance against GI nematodes in organized sheep and goat farms in Bangladesh. Appropriate measures need to be taken to overcome the situation. Asian J. Med. Biol. Res. December 2018, 4(4): 378-382

scholarly journals The impact of within-host ecology on the fitness of a drug-resistant parasite

2018 ◽  
Vol 2018 (1) ◽  
pp. 127-137 ◽  
Author(s):  
Silvie Huijben ◽  
Brian H K Chan ◽  
William A Nelson ◽  
Andrew F Read
Keyword(s):  
Drug Resistant ◽  
Resistant Parasite ◽  
Host Ecology ◽  
The Impact ◽  
Drug Resistant Parasite

scholarly journals Mechanism of Amphotericin B Resistance in Clinical Isolates of Leishmania donovani

2011 ◽  
Vol 56 (2) ◽  
pp. 1031-1041 ◽  
Author(s):  
Bidyut Purkait ◽  
Ashish Kumar ◽  
Nilay Nandi ◽  
Abul Hasan Sardar ◽  
Sushmita Das ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Metabolic Pathway ◽  
Resistant Strain ◽  
Leishmania Donovani ◽  
Expression Patterns ◽  
Sensitive Strain ◽  
Clinical Isolates ◽  
Membrane Composition ◽  
Clinical Value ◽  
Resistant Parasite

ABSTRACTThe clinical value of amphotericin B, the mainstay therapy for visceral leishmaniasis in sodium antimony gluconate-nonresponsive zones of Bihar, India, is now threatened by the emergence of acquired drug resistance, and a comprehensive understanding of the underlying mechanisms is the need of the hour. We have selected an amphotericin B-resistant clinical isolate which demonstrated 8-fold-higher 50% lethal doses (LD50) than an amphotericin B-sensitive strain to explore the mechanism of amphotericin B resistance. Fluorimetric analysis demonstrated lower anisotropy in the motion of the diphenylhexatriene fluorescent probe in the resistant strain, which indicated a higher fluidity of the membrane for the resistant strain than for the sensitive strain. The expression patterns of the two transcripts ofS-adenosyl-l-methionine:C-24-Δ-sterol methyltransferase and the absence of ergosterol, replaced by cholesta-5,7,24-trien-3β-ol in the membrane of the resistant parasite, indicate a decreased amphotericin B affinity, which is evidenced by decreased amphotericin B uptake. The expression level of MDR1 is found to be higher in the resistant strain, suggesting a higher rate of efflux of amphotericin B. The resistant parasite also possesses an upregulated tryparedoxin cascade and a more-reduced intracellular thiol level, which helps in better scavenging of reactive oxygen species produced by amphotericin B. The resistance to amphotericin B was partially reverted by the thiol metabolic pathway and ABC transporter inhibitors. Thus, it can be concluded that altered membrane composition, ATP-binding cassette transporters, and an upregulated thiol metabolic pathway have a role in conferring amphotericin B resistance in clinical isolates ofLeishmania donovani.

scholarly journals Synthesis and Antimalarial Activity of 4-Methylaminoquinoline Compounds against Drug-Resistant Parasite

ACS Omega ◽  
2021 ◽  
Author(s):  
Vinay Shankar Tiwari ◽  
Prince Joshi ◽  
Kanchan Yadav ◽  
Anamika Sharma ◽  
Sushobhan Chowdhury ◽  
...  
Keyword(s):  
Antimalarial Activity ◽  
Drug Resistant ◽  
Resistant Parasite ◽  
Drug Resistant Parasite

scholarly journals Amodiaquine resistance in Plasmodium berghei is associated with PbCRT His95Pro mutation, loss of chloroquine, artemisinin and primaquine sensitivity, and high transcript levels of key transporters

2017 ◽  
Vol 2 ◽  
pp. 44 ◽  
Author(s):  
Loise Ndung'u ◽  
Benard Langat ◽  
Esther Magiri ◽  
Joseph Ng'ang'a ◽  
Beatrice Irungu ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Malaria Parasite ◽  
Pcr Amplification ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Effective Dosage ◽  
Cross Resistance ◽  
Multidrug Resistance Gene ◽  
Resistant Parasite ◽  
Long Acting

Background: The human malaria parasite Plasmodium falciparum has evolved complex drug evasion mechanisms to all available antimalarials. To date, the combination of amodiaquine-artesunate is among the drug of choice for treatment of uncomplicated malaria. In this combination, a short acting, artesunate is partnered with long acting, amodiaquine for which resistance may emerge rapidly especially in high transmission settings. Here, we used a rodent malaria parasite Plasmodium berghei ANKA as a surrogate of P. falciparum to investigate the mechanisms of amodiaquine resistance. Methods: We used serial technique to select amodiaquine resistance by submitting the parasites to continuous amodiaquine pressure. We then employed the 4-Day Suppressive Test to monitor emergence of resistance and determine the cross-resistance profiles. Finally, we genotyped the resistant parasite by PCR amplification, sequencing and relative quantitation of mRNA transcript of targeted genes. Results: Submission of P. berghei ANKA to amodiaquine pressure yielded resistant parasite within thirty-six passages. The effective dosage that reduced 90% of parasitaemia (ED90) of sensitive line and resistant line were 4.29mg/kg and 19.13mg/kg, respectively. After freezing at -80ºC for one month, the resistant parasite remained stable with an ED90 of 18.22mg/kg. Amodiaquine resistant parasites are also resistant to chloroquine (6fold), artemether (10fold), primaquine (5fold), piperaquine (2fold) and lumefantrine (3fold). Sequence analysis of Plasmodium berghei chloroquine resistant transporter revealed His95Pro mutation. No variation was identified in Plasmodium berghei multidrug resistance gene-1 (Pbmdr1), Plasmodium berghei deubiquitinating enzyme-1 or Plasmodium berghei Kelch13 domain nucleotide sequences. Amodiaquine resistance is also accompanied by high mRNA transcripts of key transporters; Pbmdr1, V-type/H+ pumping pyrophosphatase-2 and sodium hydrogen ion exchanger-1 and Ca2+/H+ antiporter. Conclusions: Selection of amodiaquine resistance yielded stable “multidrug-resistant’’ parasites and thus may be used to study common resistance mechanisms associated with other antimalarial drugs. Genome wide studies may elucidate other functionally important genes controlling AQ resistance in P. berghei.

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