Monitoring Plasmodium vivax resistance to antimalarials: Persisting challenges and future directions

Autor: Simone Ladeia-Andrade, Rodrigo M. Corder, Marcelo U. Ferreira, Gabriel W. Rangel, Igor Cavallini Johansen, Taís Nóbrega de Sousa, José Pedro Gil
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Primaquine
Ex vivo assays
Plasmodium vivax
CQ
chloroquine
pvmdr-1
Plasmodium vivax multidrug resistance 1
Drug resistance
Infectious and parasitic diseases
RC109-216
G6PD
glucose-6-phosphate dehydrogenase
0302 clinical medicine
Chloroquine
MEDICAMENTO
TBM
transmembrane domain
Pharmacology (medical)
biology
SP
sulphadoxine-pyrimethamine
Special issue articles on 'Drug Resistance'
Infectious Diseases
cPQ
carboxyprimaquine
SNP
single-nucleotide polymorphism
medicine.drug
medicine.medical_specialty
DCQ
desethylchloroquine
QN
quinine
030231 tropical medicine
EDTA
ethylenediamine tetraacetic acid
03 medical and health sciences
Antimalarials
DHPS
dihydropteroate synthase
parasitic diseases
medicine
Malaria
Vivax
Humans
Intensive care medicine
Chloroquine resistance
TQ
tafenoquine
ACT
antemisinin-based combination therapy
Pharmacology
Resistance (ecology)
business.industry
pvcrt-o
Plasmodium vivax chloroquine resistance transporter ortholog
IMDM
Iscove's modified Dulbecco's medium
Molecular markers
medicine.disease
biology.organism_classification
DHFR
dihydrofolate reductase
bp
base pairs
030104 developmental biology
MAO-A
Monoamine oxidase A
CYP2D6
cytochrome P450 2D6
DEN
dextromethorphan
PQ
primaquine
Parasitology
business
Malaria
MQ
mefloquine
Clinical studies
Zdroj: International Journal for Parasitology: Drugs and Drug Resistance, Vol 15, Iss, Pp 9-24 (2021)
International Journal for Parasitology: Drugs and Drug Resistance
Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
ISSN: 2211-3207
Popis: Emerging antimalarial drug resistance may undermine current efforts to control and eliminate Plasmodium vivax, the most geographically widespread yet neglected human malaria parasite. Endemic countries are expected to assess regularly the therapeutic efficacy of antimalarial drugs in use in order to adjust their malaria treatment policies, but proper funding and trained human resources are often lacking to execute relatively complex and expensive clinical studies, ideally complemented by ex vivo assays of drug resistance. Here we review the challenges for assessing in vivo P. vivax responses to commonly used antimalarials, especially chloroquine and primaquine, in the presence of confounding factors such as variable drug absorption, metabolism and interaction, and the risk of new infections following successful radical cure. We introduce a simple modeling approach to quantify the relative contribution of relapses and new infections to recurring parasitemias in clinical studies of hypnozoitocides. Finally, we examine recent methodological advances that may render ex vivo assays more practical and widely used to confirm P. vivax drug resistance phenotypes in endemic settings and review current approaches to the development of robust genetic markers for monitoring chloroquine resistance in P. vivax populations.
Graphical abstract Image 1
Highlights • Plasmodium vivax resistance to chloroquine may undermine malaria elimination efforts. • Plasmodium vivax resistance to schizontocides has been mostly monitored in therapeutic efficacy studies. • In vivo studies to determine the anti-relapse efficacy of primaquine are challenging to design and execute. • Ex vivo assays to determine Plasmodium vivax resistance to schizontocides remain limited to research settings. • Robust molecular markers to monitor Plasmodium vivax drug resistance are currently lacking.
Databáze: OpenAIRE
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