scholarly journals P. falciparum PfATP4 Multi-Drug Resistance Resistance to KAE609 (Cipargamin) is Present in Africa

2018 ◽  
Author(s):  
James McCulloch
Keyword(s):  
Drug Resistance ◽  
Clinical Trials ◽  
Plasmodium Falciparum ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Blood Stage ◽  
Policy Implications ◽  
Multi Drug Resistance ◽  
Drug Resistant ◽  
Important Policy

AbstractThe PfATP4 (PF3D7 1211900) multi-drug resistance mutation G223R is found in Africa by genetically analyzing 2640 worldwide Plasmodium falciparum blood stage isolates (the MalariaGen Pf3k resource). This mutation confers an approximate 8 fold [4] increase in the PfATP4 IC50 of Spiroindolones (KAE609 & KAE678) [14],[16],[4],[10] and Aminopyrazoles (GNF-Pf4492) [4]. It is postulated that the G223R mutation may be a consequence of the drug resistant Southeast Asian Dd2 genotype becoming more dominant in Africa [3]. The presence of this mutation has important policy implications for the eventual general deployment of the Spiroindolone KAE609 (Cipargamin) which is currently undergoing stage 2 clinical trials.

scholarly journals Assessing the Cost-Benefit Effect of a Plasmodium falciparum Drug Resistance Mutation on Parasite Growth In Vitro

2012 ◽  
Vol 57 (2) ◽  
pp. 887-892 ◽  
Author(s):  
G. Froberg ◽  
P. E. Ferreira ◽  
A. Martensson ◽  
A. Ali ◽  
A. Bjorkman ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Resistance Mutation ◽  
Cost Benefit ◽  
Drug Resistance Mutation ◽  
Parasite Growth ◽  
The Cost

scholarly journals Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap–Core Interface of HIV-1 Protease

ACS Omega ◽  
2018 ◽  
Vol 3 (9) ◽  
pp. 12132-12140 ◽  
Author(s):  
Andres Wong-Sam ◽  
Yuan-Fang Wang ◽  
Ying Zhang ◽  
Arun K. Ghosh ◽  
Robert W. Harrison ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Hiv 1

scholarly journals Update on TB Vaccine Pipeline

2020 ◽  
Vol 10 (7) ◽  
pp. 2632 ◽  
Author(s):  
Carlos Martin ◽  
Nacho Aguilo ◽  
Dessislava Marinova ◽  
Jesus Gonzalo-Asensio
Keyword(s):  
Drug Resistance ◽  
Clinical Trials ◽  
Mycobacterium Tuberculosis ◽  
Infectious Diseases ◽  
Significant Role ◽  
Causes Of Death ◽  
Multi Drug Resistance ◽  
Bacillus Calmette Guerin ◽  
The World

In addition to antibiotics, vaccination is considered among the most efficacious methods in the control and the potential eradication of infectious diseases. New safe and effective vaccines against tuberculosis (TB) could be a very important tool and are called to play a significant role in the fight against TB resistant to antimicrobials. Despite the extended use of the current TB vaccine Bacillus Calmette-Guérin (BCG), TB continues to be transmitted actively and continues to be one of the 10 most important causes of death in the world. In the last 20 years, different TB vaccines have entered clinical trials. In this paper, we review the current use of BCG and the diversity of vaccines in clinical trials and their possible indications. New TB vaccines capable of protecting against respiratory forms of the disease caused by sensitive or resistant Mycobacterium tuberculosis strains would be extremely useful tools helping to prevent the emergence of multi-drug resistance.

scholarly journals Monitoring of HIV Drug Resistance Mutations in Newly Diagnosed Patients in Cyprus (2010–2012)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S424-S424
Author(s):  
Ioannis Demetriades
Keyword(s):  
Drug Resistance ◽  
Phylogenetic Trees ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
High Rate ◽  
Resistance Testing ◽  
Newly Diagnosed ◽  
Resistance Mutations ◽  
Subtype B ◽  
Hiv 1

Abstract Background A molecular epidemiology study of HIV-1 infection was conducted in 100 HIV-1 diagnosed and untreated patients in Cyprus representing 65.4 percent of all the reported HIV-1 infections in Cyprus between 2010 and 2012. Methods Eighty-two patients were newly diagnosed (genotypic drug resistance testing within six months from diagnosis), and 18 patients were HIV-1 diagnosed for a longer period or the diagnosis date was unknown. Results Phylogenetic trees of the pol sequences obtained in this study with reference sequences indicated that subtypes B and A1 were the most common subtypes present and accounted for 41.0 and 19.0% respectively, followed by subtype C (7.0%), F1 (8.0%), CRF02_AG (4.0%), A2 (2.0%), other CRFs (7.0%) and unknown recombinant forms, URFs (12%). Most of newly-diagnosed study subjects were Cypriots (63%), males (78%) with median age 39 (Interquartile Range, IQR 33–48) reporting having sex with other men, MSM (51%). Conclusion A high rate of clustered transmission of subtype B drug-sensitive strains to reverse transcriptase and protease inhibitors was observed among MSM. Twenty-eight out of forty-one MSM study subjects (68.0%) infected were implicated in five transmission clusters, two of which are subtype A1 and three subtype B strains. The two largest MSM subtype B clusters included nine and eight Cypriot men, respectively, living in all major cities in Cyprus. There were only three newly diagnosed patients with transmitted drug resistant HIV-1 strains, one study subject from the United Kingdom infected with subtype B strain and one from Romania with subtype A2 strain, both with the PI drug resistance mutation M46L and one patient from Greece with subtype A1 strain with the NNRTI drug resistance mutation K103N. Disclosures All authors: No reported disclosures.

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