In vitro chloroquine resistance for Plasmodium vivax isolates from the Western Brazilian Amazon

Malaria Journal

Research

Fátima Nogueira¹  Henrique Silveira¹  Monica RF Costa²  Jacqueline S Costa²  Yonne F Chehuan²  Gisely C Melo³  Maria GC Alecrim³  Larissa W Brasil³  Wuelton M Monteiro³  Marcus VG Lacerda⁴ 

[1] Centro de Malária e Outras Doenças Tropicais, UEI Malária, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira, 100, 1349-008, Lisbon, Portugal;Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25, Dom Pedro, 69040-000, Manaus, AM, Brazil;Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25, Dom Pedro, 69040-000, Manaus, AM, Brazil;Universidade do Estado do Amazonas, Av. Pedro Teixeira, 25, 69040-000, Dom Pedro, Manaus, AM, Brazil;Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25, Dom Pedro, 69040-000, Manaus, AM, Brazil;Universidade do Estado do Amazonas, Av. Pedro Teixeira, 25, 69040-000, Dom Pedro, Manaus, AM, Brazil;Universidade Nilton Lins, Av. Prof. Nilton Lins, 3259, 69058-030, Parque das Laranjeiras, Manaus, AM, Brazil;

关键词: Malaria;    Plasmodium Vivax;    Chloroquine;    Mefloquine;    Resistance;    Treatment;   

DOI  :  10.1186/1475-2875-12-226

 received in 2013-03-25, accepted in 2013-06-24,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundChloroquine (CQ) and primaquine (PQ) are still the drugs of choice to treat Plasmodium vivax malaria in many endemic areas, Brazil included. There is in vivo evidence for the P. vivax resistance to CQ in the Brazilian Amazon, where the increase in the proportion of P. vivax malaria parallels the increase of unusual clinical complications related to this species. In this study, in vitro CQ and mefloquine (MQ)-susceptibility of P. vivax isolates from the Western Brazilian Amazon was tested using the double-site enzyme-linked lactate dehydrogenase immunodetection (DELI) assay.MethodsA total of 112 P. vivax isolates were tested in vitro for CQ-susceptibility and out of these 47 were also tested for MQ-susceptibility. The DELI assay was used to detect P. vivax growth at 48-hour short-term culture in isolates with ring stages ranging from 50 to %. Each isolate was tested in triplicate and geometric means of IC50’s was obtained. Nineteen isolates were genetically characterized for pvdhfr, pvmrp1, pvmdr1 and pvdhps candidate genes likely related to CQ resistance (10 with IC50<40 nM and 9 with IC50 >100 nM).ResultsTwelve out of 112 isolates were considered resistant to CQ, resulting in 10.7% (IC95% 5.0-16.4), while 3 out of 47 (6.4%; IC95% 0.0-12.8) were resistant to MQ. A discrete correlation was observed between IC50’s of CQ and MQ (Spearman=0.294; p=0.045). For pvdhps gene, a non-synonymous mutation was found at codon 382 (S→C) in 5/8 CQ-sensitive samples and 1/9 CQ-resistant samples (p=0.027). The other molecular markers were not associated to CQ-susceptibility.ConclusionsIn vitro CQ-resistance estimated in this study, estimated by the DELI test, was very similar to that observed in clinical trials, suggesting that in vitro procedures developed by capable local laboratories are useful in the surveillance of CQ-resistance in the Amazon; concurrent Amazon P. vivax strains with both CQ and MQ resistance may be common; and a non-synonymous mutation at pvdhps codon 382 (S→C) was associated to in vitro susceptibility to CQ, needing further studies to be confirmed.

【 授权许可】

Unknown   
© Chehuan et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.