Resistance to Antimalarial Drugs: Parasite and Host Genetic Factors

Mehlotra, Rajeev K.; Zimmerman, Peter A.

doi:10.1007/0-387-28295-5_5

Cited by 5 publications

(2 citation statements)

References 281 publications

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“…CQ, SP and more recently the artemisinin class drugs have been widely adopted as first-line drugs because they are highly efficacious in eliminating P. falciparum -infected erythrocytes and they are well tolerated by almost all patients [11,12]. In addition, unlike other drugs such as atovaquone and pyrimethamine (when not combined with sulfadoxine), the rate at which de novo mutations conferring resistance occur is low.…”

Section: Drug Selection Of Resistant Parasitesmentioning

confidence: 99%

Antimalarial drug resistance: a review of the biology and strategies to delay emergence and spread

Klein¹

2013

International Journal of Antimicrobial Agents

114

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The emergence of resistance to former first-line antimalarial drugs has been an unmitigated disaster. In recent years, artemisinin class drugs have become standard and they are considered an essential tool for helping to eradicate the disease. However, their ability to reduce morbidity and mortality and to slow transmission requires the maintenance of effectiveness. Recently, an artemisinin delayed-clearance phenotype was described. This is believed to be the precursor to resistance and threatens local elimination and global eradication plans. Understanding how resistance emerges and spreads is important for developing strategies to contain its spread. Resistance is the result of two processes: (i) drug selection of resistant parasites; and (ii) the spread of resistance. In this review, we examine the factors that lead to both drug selection and the spread of resistance. We then examine strategies for controlling the spread of resistance, pointing out the complexities and deficiencies in predicting how resistance will spread.

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Section: Drug Selection Of Resistant Parasitesmentioning

confidence: 99%

Antimalarial drug resistance: a review of the biology and strategies to delay emergence and spread

Klein¹

2013

International Journal of Antimicrobial Agents

114

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“…By measuring the proguanil: cycloguanil metabolic ratio and/or the ability of CYP2C19 to metabolize a probe drug, ( S )-mephenytoin, the poor metabolism (PM) and extensive metabolism (EM) phenotypes are identified [70]. The prevalence of the PM phenotype varies substantially among ethnically different populations (Table 3) [100,101], and two variant alleles, CYP2C19*2 and CYP2C19*3 , are largely associated with the PM phenotype [102]. …”

Section: Antimalarial Drug Metabolism In the Human Hostmentioning

confidence: 99%

Application of Pharmacogenomics to Malaria: A Holistic Approach for Successful Chemotherapy

2009

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Drug resistance in malaria jeopardizes the most elementary objectives of malaria control – reducing suffering and eliminating mortality. An important, and so far the only known, mechanism of drug resistance appears to be polymorphisms in the malaria parasite genes. Efforts to circumvent antimalarial drug resistance now range from the use of combination therapies with existing agents to genomics-based studies directed toward discovering novel targets and agents. However, the potential contribution of host genetic/molecular factors, particularly those associated with antimalarial drug metabolism, remains largely unexplored. Our knowledge concerning the basic mechanisms involved in the pharmacokinetics of antimalarial drugs is fragmentary. In addition, the link between antimalarial drug pharmacokinetics and treatment outcomes is generally unclear. The purpose of this article is to provide general background information on antimalarial drug resistance and associated parasite genetic factors, and subsequently highlight the aforementioned unexplored and unclear areas, with a view to stimulate much needed further research.

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Challenges in the Control and Eradication of Malaria

Fong

2012

Challenges in Infectious Diseases

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Resistance to Antimalarial Drugs: Parasite and Host Genetic Factors

Cited by 5 publications

References 281 publications

Antimalarial drug resistance: a review of the biology and strategies to delay emergence and spread

Antimalarial drug resistance: a review of the biology and strategies to delay emergence and spread

Application of Pharmacogenomics to Malaria: A Holistic Approach for Successful Chemotherapy

Challenges in the Control and Eradication of Malaria

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