Use of a colorimetric (DELI) test for the evaluation of chemoresistance of Plasmodium falciparum and Plasmodium vivax to commonly used anti-plasmodial drugs in the Brazilian Amazon

Abstract

BackgroundThe emergence and spread of Plasmodium falciparum and Plasmodium vivax resistance to available anti-malarial drugs represents a major drawback in the control of malaria and its associated morbidity and mortality. The aim of this study was to evaluate the chemoresistance profile of P. falciparum and P. vivax to commonly used anti-plasmodial drugs in a malaria-endemic area in the Brazilian Amazon.MethodsThe study was carried out in Manaus (Amazonas state), in the Brazilian Amazon. A total of 88 P. falciparum and 178 P. vivax isolates was collected from 2004 to 2007. The sensitivity of P. falciparum isolates was determined to chloroquine, quinine, mefloquine and artesunate and the sensitivity of P. vivax isolates was determined to chloroquine and mefloquine, by using the colorimetric DELI test.ResultsAs expected, a high prevalence of P. falciparum isolates resistant to chloroquine (78.1%) was observed. The prevalence of isolates with profile of resistance or decreased sensitivity for quinine, mefloquine and artesunate was 12.7, 21.2 and 11.7%, respectively. In the case of P. vivax, the prevalence of isolates with profile of resistance for chloroquine and mefloquine was 9.8 and 28%, respectively. No differences in the frequencies of isolates with profile of resistance or geometric mean IC50s were seen when comparing the data obtained in 2004, 2005, 2006 and 2007, for all tested anti-malarials.ConclusionsThe great majority of P. falciparum isolates in the Brazilian malaria-endemic area remain resistant to chloroquine, and the decreased sensitivity to quinine, mefloquine and artesunate observed in 10–20% of the isolates must be taken with concern, especially for artesunate. Plasmodium vivax isolates also showed a significant proportion of isolates with decreased sensitivity to chloroquine (first-line drug) and mainly to mefloquine. The data presented here also confirm the usefulness of the DELI test to generate results able to impact on public health policies.

Monitoring the Efficacy of Chloroquine-Primaquine Therapy for Uncomplicated Plasmodium vivax Malaria in the Main Transmission Hot Spot of Brazil

“…Similar results were seen when the analysis was limited to isolates from the 40 participants in the clinical trial (26 allocated to treatment arm 1 and 14 allocated to arm 2), with a median IC 50 of 19.1 nM (interquartile range, 9.6 to 34.6 nM). IC 50 values of Ͼ100 nM, suggestive of CQ resistance (23), were not observed in this and another recent study in Porto Velho, Brazil (24), but had previously been found in approximately 10% of P. vivax isolates from Urabá, Colombia (25), and Manaus, Brazil (26,27) (Table 5). Day 0 parasites from patient 1/4, who had a PCR-confirmed parasite recrudescence at day 28 (Table 3), were fully sensitive to CQ (IC 50 estimate, 14.1 nM).…”

“…CQ remains the first-line treatment for uncomplicated P. vivax malaria in Brazil (28), but declining efficacy has been repeatedly characterized in the large port city of Manaus, using both in vivo (8)(9)(10) and ex vivo (26,27) assays. However, it remains undetermined whether CQ resistance has spread to other sites across the Amazon Basin and represents a major challenge for current malaria elimination in this country and its neighbors (12,29).…”

Assessment of copy number variation in genes related to drug resistance in Plasmodium vivax and Plasmodium falciparum isolates from the Brazilian Amazon and a systematic review of the literature

“…Accordingly, P. vivax resistance to MQ has been reported in the Brazilian Amazon region [16, 55, 79]. In P. falciparum , resistance to MQ has been associated with increased copy number of pfmdr1 [27].…”

Genetic diversity of chloroquine-resistant Plasmodium vivax parasites from the western Brazilian Amazon

“…In 2004/2005, 10% of P. vivax infections studied in Manaus showed an in vivo CQ-resistant (CQ-Rt) phenotype (Santana Filho et al 2007). Recently, two studies evaluated P. vivax CQ-susceptibility by using short-term in vitro cultures of samples collected in 2004-2008 from AM and confirmed the same prevalence of CQ-R among P. vivax parasites (10%) ( Chehuan et al 2013 , Pratt-Riccio et al 2013 ). In other endemic regions of Brazil, such as in the state of Acre, no CQ-R has been reported ( Orjuela-Sánchez et al 2009 ) and no studies have been reported so far in other regions of Latin America ( Gonçalves et al 2014 ).…”