Resistance to in vivo and in vitro chemotherapies in the brazilian Amazonia

Alecrim, Maria das Graças Costa

doi:10.1590/s0074-02761986000600025

Cited by 9 publications

(9 citation statements)

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“…In order to avoid such a impairment, resistance monitoring is of uppermost importance, at best by in vivo and in vitro methods. The present study confirmed the high level of resistance to chloroquine previously demonstrated in other areas of the Amazon basin (Boulos et al 1986, Alecrim 1986, Di Santi et al 1988, Zalis et al 1998. Regarding quinine, besides the low true-resistance percentage observed (3.3%), IC 50s to the tested samples were as high as those observed in other areas of the world with decreased susceptibility (Webster et al 1985), suggesting that the usefulness of the drug will not last for a long time.…”

Section: Discussionsupporting

confidence: 90%

“…Malaria prevalence in Brazil has increased three times during the past and quinine in those studies were too low, leading to overestimation of the resistance percentages (Alecrim 1986, Di Santi et al 1988) When adequate "cut off" limits are employed, taking together in vivo and in vitro data, parasite resistance has been observed at levels greater than 70% to chloroquine, greater than 60% to sulfadoxine-pyrimethamine, lower than 20% to quinine and almost none to mefloquine (Boulos et al 1986, Alecrim 1986, Di Santi et al 1988, Kremsner et al 1989, Souza 1992, Couto et al 1993. As in vitro evaluations of P. falciparum sensitivity have not been performed since the 80's (Di Santi et al 1988, Kremsner et al 1989, and considering that radioisotopic methods had not been used, except in one occasion (Zalis et al 1998), we decided to verify the patterns of resistance in a typical endemic area of the Brazilian Amazon region.…”

mentioning

confidence: 98%

“…In vitro studies in Brazil have been conducted using morphology-techniques (Alecrim 1986, Di Santi et al 1988, Kremsner et al 1989). These techniques are less expensive than the radiosotopic ones, but are also more prone to subjective misinterpretation.…”

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confidence: 99%

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Antimalarial drug susceptibility testing of Plasmodium falciparum in Brazil using a radioisotope method

Cerutti

Marques

Alencar

et al. 1999

Mem. Inst. Oswaldo Cruz

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Section: Discussionsupporting

confidence: 90%

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confidence: 98%

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Antimalarial drug susceptibility testing of Plasmodium falciparum in Brazil using a radioisotope method

Cerutti

Marques

Alencar

et al. 1999

Mem. Inst. Oswaldo Cruz

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“…Further similar cases were reported in Brazil in the 1980s in the states of Amazonas and Maranhão [5, 6]. For this reason, an alternative therapeutic regimen that combined sulphadoxine and pyrimethamine (SP) was adopted as the first line treatment recommendation.…”

Section: Introductionmentioning

confidence: 65%

Analysis of polymorphisms in Plasmodium falciparum genes related to drug resistance: a survey over four decades under different treatment policies in Brazil

Inoue

Lopes

Rosário

et al. 2014

Malar J

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BackgroundAnti-malarial resistance in Plasmodium falciparum remains an obstacle for malaria control. Resistance-associated genes were analysed in Brazilian samples over four decades to evaluate the impact of different treatment regimens on the parasite genetic profile.MethodsSamples were collected on filter paper from patients infected in the Amazon region from 1984 to 2011. DNA was extracted with Chelex® 100 and monoinfection confirmed by PCR. SNPs in the pfcrt, pfmdr1, pfdhfr and pfdhps genes were assessed by PCR-RFLP. The pfmdr1 copy number was estimated using real time quantitative PCR with SYBR® Green. Parasite response was assessed ex vivo with seven concentrations of each anti-malarial. Patients were treated according to Brazilian guidelines: quinine plus tetracycline or mefloquine in period 1 and ACT in period 2.ResultsAll 96 samples presented the pfcrt 76T mutant throughout the assessed periods. In addition, all isolates showed ex vivo chloroquine resistance. The pfmdr1 86Y was detected in 1.5% of samples in period 1, and in 25% in period 2. All samples presented the pfmdr1 1246Y. The analysis of pfmdr1 copy number showed amplification in 37.3% in period 1 and in 42% in period 2. Mutations in pfdhfr were shown as follows: 51I in all samples in period 1 and in 81.2% in period 2; 59R in 6.4% in period 2. The pfdhfr 108N and the pfdhps 437G were seen in all samples along time; the pfdhps 540E in 93.7% in period 1 and in 75% in period 2.ConclusionsThe 76T mutation associated to chloroquine resistance is still present in the parasite population, although this anti-malarial was withdrawn from the chemotherapy of P. falciparum in Brazil in the mid-1980s. All isolates assayed ex vivo for chloroquine showed resistant phenotype and 76T. No association was observed between pfmdr1 mutations and resistance to quinine, mefloquine and artemisinin derivatives. Additionally, the pfdhfr 108N mutation was detected in all samples throughout the evaluated periods, demonstrating fixation of the mutant allele in the parasite population. Changes in Brazilian national guidelines for the malaria chemotherapy in the last 27 years yielded a discreet genetic impact in the parasite population.

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“…With the purpose of facing the challenge of quinine effectiveness decrease in Brazilian P. falciparum strains 1,2,8,9,16,26,34,41 , we evaluated the in vitro sensitivity of isolates from North Brazilian States to quinidine in comparison to quinine and chloroquine. We were based on previous studies when quinidine showed to exert antimalarial effect in concentrations many times inferior than those used in the cardiovascular therapy 23 .…”

Section: Introductionmentioning

confidence: 99%

In vitro evaluation of quinidine sensitivity in brazilian Plasmodium falciparum isolates: comparative analysis to quinine and chloroquine

Menezes

Kirchgatter

Santi

et al. 2001

Rev. Inst. Med. trop. S. Paulo

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Falciparum malaria represents a serious and an increasing world public health problem due to the acquired parasite's resistance to the most available drugs. In some endemic areas, quinidine, a diastereoisomer of the antimalarial quinine, has been employed for replacing the latter. In order to evaluate the use of quinidine as an alternative to the increasing loss of quinine effectiveness in Brazilian P. falciparum strains, as has been observed in the Amazon area, we have assayed quinidine, quinine and chloroquine. The in vitro microtechnique was employed. All isolates showed to be highly resistant to chloroquine. Resistance to quinine was not noted although high MIC (minimal inhibitory concentration) values have been observed. These data corroborate the decreasing sensitivity to quinine in strains from Brazil. Quinidine showed IC50 from 0.053 to 4.577 micromol/L of blood while IC50 from 0.053 to 8.132 micromol/L of blood was estimated for quinine. Moreover, clearance of the parasitemia was observed in concentrations lower than that used for quinidine in antiarrhythmic therapy, confirming our previous data. The results were similar to African isolate.

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Resistance to in vivo and in vitro chemotherapies in the brazilian Amazonia

Cited by 9 publications

References 0 publications

Antimalarial drug susceptibility testing of Plasmodium falciparum in Brazil using a radioisotope method

Antimalarial drug susceptibility testing of Plasmodium falciparum in Brazil using a radioisotope method

Analysis of polymorphisms in Plasmodium falciparum genes related to drug resistance: a survey over four decades under different treatment policies in Brazil

In vitro evaluation of quinidine sensitivity in brazilian Plasmodium falciparum isolates: comparative analysis to quinine and chloroquine

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