Emprego da associação tetraciclina e quinino no tratamento da malária causada pelo Plasmodium falciparum

Barata, Luiz Carlos Barradas; Boulos, Marcos; Dutra, Araripe Pacheco

doi:10.1590/s0037-86821986000300002

Cited by 6 publications

(5 citation statements)

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“…Analysis of pfcrt gene showed that all samples harboured the 76T mutation, strongly associated to chloroquine resistance, throughout the evaluated periods, even though this 4-aminoquinoline was replaced by quinine in monotherapy or associated to tetracycline in Brazilian national guidelines for malaria chemotherapy in the mid-1980s [46, 47]. Assessment of pfcrt mutations is relevant to monitor molecular changes that could have led to reversal of chloroquine resistance after drug withdrawal, as seen in Malawi.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…O quinino voltou a ser utilizado no Brasil com a disseminação de resistência do P. falciparum à cloroquina e à associação de sulfadoxina e pirimetamina, a partir de meados dos anos 80 2 .…”

Section: Discussionunclassified

Avaliação clínica do quinino para o tratamento de malária por Plasmodium falciparum

Boulos

Dutra

DiSanti

et al. 1997

Rev. Soc. Bras. Med. Trop.

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O quinino foi o primeiro medicamento correntemente usado para tratar malária, tendo sido abandonado seu emprego principalmente após o início do emprego da cloroquina. A partir da década de 60 com o surgimento de resistência do P. falciparum à cloroquina voltou-se a utilizar o quinino isolado ou em associação para tratar tal infecção. Com o objetivo de avaliar clinicamente a resposta ao quinino de pacientes com malária por P. falciparum, analisamos os prontuários de 484 pacientes atendidos no Laboratório de Malária da SUCEN e acompanhados por pelo menos 28 dias, e que haviam recebido diferentes esquemas terapêuticos com quinino isolado ou em associação. Do total, 81,0% dos pacientes foram curados pelos esquemas empregados, sendo que dos restantes apenas 0,6% foram R2 e nenhum R3. Tais resultados mostram ainda que esquemas contendo quinino podem ser adequados para tratar malária por P. falciparum.

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“…(12-1') Although in Brazil the standard treatment lor falciparum malaria, quinine (3 days) plus tetracycline (7 days), is still cff icaclous, concerns have arisen regarding side effects that may lead to poor compliancc in athome treatmcnts. (20)(21)(22) 23 Artemisinin derivatives are promising drugs against falciparum malaria, however recrudescences are often observed when they are used alone for short lrealment periods (see section 2.3.). This is because, although artemisinin derivatives slJch as oral artesunate are fast acting drugs (parasite clearance in 2 days), their half lives seem to be insufftcient to kill aIl blood parasites.…”

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confidence: 99%

“…Drug combinations have hccn extensively studied and used by natIOnal malaria control programs in many endemic areas, (17,20,(35)(36)(37)(38) e _ _ In one study in Brazil, 95% of 110 falciparum malaria patients l'rom the Amazon region were successfully treated with the comhination of quinmc plus tetracycline. (20) Since 1990, the combmation of quinme (3 days) and tetracyclinc (7 days The efficacy of 7-day and 5-day courses of oral artesunate (total dose = 0.6 g) to treat uncomplicated falciparum malaria was assessed in 80 Thai paticnts. 14 ')) In the 5-day regimen, the mean times for parasite and fever clearance were 41 and 29 hours, respectively and the cure rate was 85% ( Based on these studies, combinations of artemisinin derivatives with metloquine and tetracycline have been evaluated.…”

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confidence: 99%

Randomized Controlled Trial of Artesunate Plus Tetracycline Versus Standard Treatment (Quinine Plus Tetracycline) for Uncomplicated Plasmodium falciparum Malaria in Brazil

Duarte¹,

Fontes²,

Gyorkos³

et al. 1996

The American Journal of Tropical Medicine and Hygiene

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A triple 'blind randomized controlled trial was undertaken in a Brazilian Amazon region (Cuiabâ-MT), tn compare the effect;veness and side effects of oral artcsunate (7 days, total dose = 0.75 g) plus tetraeycline (7 days, total dose = 10.5 g) [AT) and oral quinine (3 days, total dose = 6 g) plus te(racydine (7 days, total dose = 10.5 g) [QT). Eligible patients had uncomph'c'ated P. falciparum malaria; age ~ 14 years; no previous malaria treatment related to ,the present attack; and, if women, indil,ation of absence of pregnancy. Clinical i\'lOEm and blood tests were pcrformt:d at baselinc (day 0) and thereafter at days 2, ·,l, 7, 14 and 28. EOE.:ctiveness was asscssed by cure rates (WHO criteria) and parasite dl!arance at day 2.176 patients were randomized, 88 to each group. 9\.\.1.6% of the AT group and 93.2% of the QT group completed the 7-day treatment. 81.8% of the AT group and 78.4% of the QT group completed follow-up visits to day 2g Groups had similar clinical characteristics at baseline. The incidence of side effects was much higher in the QT group (82%) th?n in the AT group (50%) [p 14 ans, aucun tnlltement antipaludéen relié à la crise présente; en cas de femmes, aucune 'ossesse indiquée. Un examen clinique et des prises de sang ont été faits au départ (jour 0) puis aux jours 2, 4, 7, 14· et 28 suivants. L'efficacité a été évaluée par les fréquences de guénson Il is to my family that 1 dedicate this thesis.'É dificil expressar min.~a gradidao à pessoas que, embora distante, se lïzeram as mais presentes durante meu perfodo na McGi11.Meu agradecimento e carinho para minha mae e mclhor amiga. Barhara, quem me deu motivaçao e auto-confiança para ir em [rente nas mais malucas situaçoes cm que me coloco, e me ensinou dedicaçâo através ùe seu proprio cxemplo ùe vida.Também quero dividir esta conquista corn minhas irmàs e irmàos, Eliane, Elisa.Elisete, Luiz e Waldeck Junior. tia e segunda mae. Neuza, meu pai, Waldc(,;k, c meus av6s, Archanjo e Elisa (em mem6ria). Pessoas que sempre foram so sorriso e carinho.

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Emprego da associação tetraciclina e quinino no tratamento da malária causada pelo Plasmodium falciparum

Cited by 6 publications

References 4 publications

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

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

Avaliação clínica do quinino para o tratamento de malária por Plasmodium falciparum

Randomized Controlled Trial of Artesunate Plus Tetracycline Versus Standard Treatment (Quinine Plus Tetracycline) for Uncomplicated Plasmodium falciparum Malaria in Brazil

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