Plasmodium falciparum malarial parasites from Brazil lack artemisinin resistance-associated mutations in the kelch13 gene

Chapadense, Francesca Guaracyaba Garcia; Machado, Ricardo Luiz Dantas; Ventura, Ana Maria Revorêdo da Silva; Areas, André Luiz Lisboa; Machado, Renato; Viana, Giselle Rachid; Zalis, Mariano Gustavo; Castro, Ana Maria de; Cravo, Pedro Vitor Lemos

doi:10.1590/0037-8682-0225-2018

Cited by 3 publications

(1 citation statement)

References 9 publications

(12 reference statements)

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“…However, previous studies in the country showed a decrease in ex vivo parasite susceptibility to amodiaquine and chloroquine overtime, and rarer to ART 8 . Reduced in vitro drug susceptibilities have been associated with non-synonymous mutations in pfcrt (chloroquine, amodiaquine, piperaquine and quinine), pfmdr1 (chloroquine, amodiaquine lumefantrine, and me oquine), pfdhfr (pyrimethamine, proguanil), pfdhps (sulfonamide, sulfadoxine, sulfone, and dapsone) and pfkelch13 (ART and its derivatives) [9][10][11][12] . This situation could therefore jeopardize the successes that have led to a reduction in the proportion of malaria morbidity -the proportion of malaria morbidity fell from 35.72% of clinical cases in 2001 to 3.29% of con rmed cases in Senegal in 2016 13 .…”

Section: Introductionmentioning

confidence: 99%

Ex vivo susceptibility and molecular signature assessment of antimalarial-based combination therapies (ACT) partner drugs resistance in Senegal

YADE

Fall

Coppée

et al. 2023

Preprint

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Background Over the last decades, Plasmodium falciparum – the main causative agent of malaria – has constantly developed resistance to antimalarial drugs such as chloroquine, sulfadoxine-pyrimethamine or artemisinin derivatives. Therefore, active surveillance in the ex vivo susceptibility to the antimalarial drugs used as partner drugs in artemisinin-based combination therapies (the current frontline antimalarial) such as amodiaquine, lumefantrine or piperaquine, is essential. Methods Here, we evaluated the ex vivo susceptibility, expressed with the ex vivo SYBR™ Green, to six antimalarial drugs (amodiaquine, chloroquine, lumefantrine, mefloquine, piperaquine and quinine) from 34 P. falciparum isolates collected in 2018 in Thiès (Senegal). Whole-genome sequencing (WGS) was used to search for mutations in P. falciparum genes known to be associated with drug resistance. Results P. falciparum isolates showed reduced ex vivo susceptibility only to chloroquine (16% of the isolates). Mutations in pfcrt K76T (21%) and pfmdr1 Y184F (53%) were the most prevalent. A significant correlation was observed between the mutants pfcrt 76T and pfmdr1 184F and IC50 values for chloroquine. A significant decrease in ex vivo susceptibility to chloroquine and quinine associated with the pfcrt R371I was also detected (P < 0.001). Conclusion Our results suggest that the ex vivo susceptibility of P. falciparum isolates to amodiaquine, lumefantrine, mefloquine, piperaquine and quinine remains high in Thiès. Directly measuring ex vivo parasite drug response and sequencing resistance mutations overtime are both useful tools for monitoring parasite drug response in field samples.

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Section: Introductionmentioning

confidence: 99%

Ex vivo susceptibility and molecular signature assessment of antimalarial-based combination therapies (ACT) partner drugs resistance in Senegal

YADE

Fall

Coppée

et al. 2023

Preprint

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Kelch13 mutations in Plasmodium falciparum and risk of spreading in Amazon basin countries

Mathieu

Singh

Monteiro

et al. 2021

Journal of Antimicrobial Chemotherapy

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Background The first potential focus for artemisinin resistance in South America was recently confirmed with the presence of the C580Y mutation in the Plasmodium falciparum kelch 13 gene (pfk13) in Guyana. Objectives This study aimed to strengthen pfk13 monitoring in the Amazon basin countries, to compile the available data and to evaluate the risk of spreading of mutations. Methods Sanger sequencing was done on 862 samples collected between 1998 and 2019, and a global map of pfk13 genotypes available for this region was constructed. Then, the risk of spreading of mutations based on P. falciparum case importation between 2015 and 2018 within countries of the Amazon basin was evaluated. Results No additional pfk13 C580Y foci were identified. Few mutations (0.5%, 95% CI = 0.3%–0.8%) in the propeller domain were observed in the general parasite population of this region despite a high proportion of K189T mutations (49.1%, 95% CI = 46.2%–52.0%) in the non-propeller domain. Case information revealed two patterns of intense human migration: Venezuela, Guyana and the Roraima State in Brazil; and French Guiana, Suriname and the Amapá State in Brazil. Conclusions There are few pfk13 mutant foci, but a high risk of dispersion in the Amazon basin, mainly from the Guiana Shield, proportionate to mining activities. Therefore, access to prompt diagnosis and treatment, and continuous molecular monitoring is essential in these geographical areas.

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Caracterización molecular del dominio de la hélice del gen k13 de Plasmodium falciparum en muestras de comunidades nativas de Condorcanqui, Amazonas, Perú

Sandoval-Bances,

Saavedra-Samillán,

Huyhua-Gutiérrez

et al. 2023

biomedica

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Introducción. La resistencia de Plasmodium falciparum a diferentes fármacos antipalúdicos es un obstáculo para eliminar la enfermedad. El genotipo resistente de P. falciparum a la artemisinina puede evaluarse examinando los polimorfismos en el dominio de la hélice del gen Pfk13. La Organización Mundial de la Salud recomienda utilizar estas mutaciones como marcadores moleculares para detectar la resistencia a la artemisinina en países donde la malaria por P. falciparum es endémica.Objetivo. Identificar mutaciones relacionadas con la resistencia a artemisinina presentes en el dominio de la hélice del gen k13 de P. falciparum.Materiales y métodos. Mediante la detección pasiva de casos, se recolectaron 51 muestras positivas por microscopía para Plasmodium, provenientes de seis comunidades del distrito de Río Santiago en Condorcanqui, Amazonas. Se realizó la confirmación molecular de la especie mediante PCR en tiempo real y el dominio de la hélice del gen Pfk13 se amplificó y secuenció por electroforesis capilar. Las secuencias obtenidas se compararon con la cepa de referencia 3D7 de fenotipo silvestre.Resultados. Se confirmó un total de 51 muestras positivas para P. falciparum, provenientes de las comunidades de Ayambis, Chapiza, Palometa, Muchinguis, Alianza Progreso y Caterpiza. Después del alineamiento de las secuencias de ADN, se determinó que las muestras no presentaron mutaciones asociadas con resistencia en el gen K13. Discusión. Los resultados obtenidos son coherentes con estudios similares realizados en otros países de Sudamérica, incluyendo Perú. Estos datos proporcionan una línea base para la vigilancia molecular de resistencia a artemisinina en la región Amazonas y refuerzan la eficacia de la terapia combinada con artemisinina en esta área.

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Plasmodium falciparum malarial parasites from Brazil lack artemisinin resistance-associated mutations in the kelch13 gene

Cited by 3 publications

References 9 publications

Ex vivo susceptibility and molecular signature assessment of antimalarial-based combination therapies (ACT) partner drugs resistance in Senegal

Ex vivo susceptibility and molecular signature assessment of antimalarial-based combination therapies (ACT) partner drugs resistance in Senegal

Kelch13 mutations in Plasmodium falciparum and risk of spreading in Amazon basin countries

Caracterización molecular del dominio de la hélice del gen k13 de Plasmodium falciparum en muestras de comunidades nativas de Condorcanqui, Amazonas, Perú

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