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chloroquine resistance

NOT Open Access | Synthesis and biological evaluation of benzhydryl-based antiplasmodial agents possessing Plasmodium falciparum chloroquine resistance transporter (PfCRT) inhibitory activity

April 6, 2021 - 14:20 -- NOT Open Access
Author(s): 
Relitti N, Federico S, Pozzetti L, Campiani G, et al.
Reference: 
Eur J Med Chem. 2021 Apr 5;215:113227

Due to the surge in resistance to common therapies, malaria remains a significant concern to human health worldwide. In chloroquine (CQ)-resistant (CQ-R) strains of Plasmodium falciparum, CQ and related drugs are effluxed from the parasite's digestive vacuole (DV). This process is mediated by mutant isoforms of a protein called CQ resistance transporter (PfCRT). CQ-R strains can be partially re-sensitized to CQ by verapamil (VP), primaquine (PQ) and other compounds, and this has been shown to be due to the ability of these molecules to inhibit drug transport via PfCRT.

The natural function of the malaria parasite's chloroquine resistance transporter

August 10, 2020 - 15:45 -- Open Access
Author(s): 
Shafik SH, Cobbold SA, Barkat K, Richards SN, Lancaster NS, Llinás M, Hogg SJ, Summers RL, McConville MJ, Martin RE
Reference: 
Nat Commun. 2020 Aug 6; 11(1):3922

The Plasmodium falciparum chloroquine resistance transporter (PfCRT) is a key contributor to multidrug resistance and is also essential for the survival of the malaria parasite, yet its natural function remains unresolved. We identify host-derived peptides of 4-11 residues, varying in both charge and composition, as the substrates of PfCRT in vitro and in situ, and show that PfCRT does not mediate the non-specific transport of other metabolites and/or ions.

Population genomics identifies a distinct Plasmodium vivax population on the China-Myanmar border of Southeast Asia

August 5, 2020 - 14:17 -- Open Access
Author(s): 
Brashear AM, Fan Q, Hu Y, Li Y, Zhao Y, Wang Z, Cao Y, Miao J, Barry A, Cui L.
Reference: 
PLoS Negl Trop Dis 14(8): e0008506

Plasmodium vivax has become the predominant malaria parasite and a major challenge for malaria elimination in the Greater Mekong Subregion (GMS). Yet, our knowledge about the evolution of P. vivax populations in the GMS is fragmental. We performed whole genome sequencing on 23 P. vivax samples from the China-Myanmar border (CMB) and used 21 high-coverage samples to compare to over 200 samples from the rest of the GMS.

NOT Open Access | Chemical profiling and quantification of potential active constituents responsible for the antiplasmodial activity of Cissampelos pareira

July 30, 2020 - 13:59 -- NOT Open Access
Author(s): 
Bhatt V, Kumari S, Upadhyay P, Agrawal P, Anmol, Sahal D, Sharma U
Reference: 
J Ethnopharmacol. 2020 Jul 26:113185

Cissampelos pareira is used traditionally in India as a remedy for the treatment of various diseases including malaria but the active ingredients responsible for antiplasmodial activity have not yet been investigated.

NOT Open Access | Altered Drug Transport by Plasmodium Falciparum Chloroquine Resistance Transporter Isoforms Harboring Mutations Associated with Piperaquine Resistance

June 29, 2020 - 16:27 -- NOT Open Access
Author(s): 
Riegel BE, Roepe PD
Reference: 
Biochemistry. 2020 Jun 26

Patterns of multiple amino acid substitutions in the Plasmodium falciparum chloroquine resistance transporter (PfCRT; UniProtKB - Q8IBZ9) have previously been shown to mediate chloroquine resistance (CQR) in P. falciparum malarial parasites. Recent reports suggest that novel mutations in PfCRT may mediate resistance to piperaquine (PPQ), which is used extensively as a partner drug in one prominent artemisinin combination therapy (ACT).

Epidemiology of malaria and chloroquine resistance in Mizoram, northeastern India, a malaria-endemic region bordering Myanmar

March 3, 2020 - 12:44 -- Open Access
Author(s): 
Rita Zomuanpuii, Christopher L. Hmar, Khawlhring Lallawmzuala, Lal Hlimpuia, Praveen Balabaskaran Nina and Nachimuthu Senthil Kumar
Reference: 
Malaria Journal 2020 19:95, 27 February 2020

Mizoram, a northeastern state in India, shares international borders with Myanmar and Bangladesh and is considered to be one of the key routes through which drug-resistant parasites of Southeast Asia enter mainland India. Despite its strategic location and importance, malaria epidemiology and molecular status of chloroquine resistance had not been well documented, and since chloroquine (CQ), as the first-line treatment in Plasmodium falciparum infection was discontinued since 2008, it was expected that CQ-sensitive haplotype would be more abundant.

En-route to the ‘elimination’ of genotypic chloroquine resistance in Western and Southern Zambia, 14 years after chloroquine withdrawal

December 9, 2019 - 16:25 -- Open Access
Author(s): 
Lungowe Sitali, Mulenga C. Mwenda, John M. Miller, Daniel J. Bridges, Moonga B. Hawela, Elizabeth Chizema-Kawesha, James Chipeta and Bernt Lindtjørn
Reference: 
Malaria Journal 2019 18:391, 3 December 2019

Anti-malarial resistance is, and continues to be a significant challenge in the fight against malaria and a threat to achieving malaria elimination. In Zambia, chloroquine (CQ), a safe, affordable and well-tolerated drug, was removed from use in 2003 due to high levels of resistance evidenced with treatment failure. This study sought to investigate the prevalence of chloroquine resistance markers in Southern and Western Provinces of Zambia 14 years after the withdrawal of CQ.

Plasmodium knowlesi as a model system for characterising Plasmodium vivax drug resistance candidate genes

June 11, 2019 - 15:08 -- Open Access
Author(s): 
Lisa H. Verzier, Rachael Coyle, Shivani Singh, Theo Sanderson, Julian C. Rayner
Reference: 
PLoS Negl Trop Dis 13(6): e0007470

Plasmodium vivax causes the majority of malaria outside Africa, but is poorly understood at a cellular level partly due to technical difficulties in maintaining it in in vitro culture conditions.

Chloroquine resistance is associated to multi-copy pvcrt-o gene in Plasmodium vivax malaria in the Brazilian Amazon

July 17, 2018 - 15:59 -- Open Access
Author(s): 
Siuhelem Rocha Silva, Anne Cristine Gomes Almeida, Gisely Cardoso de Melo, et al.
Reference: 
Malaria Journal 2018 17:267, 16 July 2018

This was the first study with 42-day clinical follow-up to evaluate the variation of the number of copies and polymorphisms in the promoter region of the pvcrt-o and pvmdr1 genes in relation to treatment outcomes.

Medical Condition: 

Therapeutic assessment of chloroquine–primaquine combined regimen in adult cohort of Plasmodium vivax malaria from a tertiary care hospital in southwestern India

August 12, 2015 - 13:22 -- Open Access
Author(s): 
Kumar Rishikesh, Asha Kamath, Manjunatha H Hande, Sudha Vidyasagar, Raviraja V Acharya, Vasudeva Acharya, Jayaprakash Belle, Ananthakrishna B Shastry, Kavitha Saravu
Reference: 
Malaria Journal 2015, 14:310 (11 August 2015)

CQ–PQ combined regimen remains outstandingly effective for uncomplicated P. vivax malaria and should be retained as treatment of choice in the study region.

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