Atovaquone, chloroquine, primaquine, quinine and tetracycline: antiproliferative effects of relevant antimalarials on Neospora caninum / Atovaquona, cloroquina, primaquina, quinino e tetraciclina: efeitos antiproliferativos de antimaláricos relevantes em Neospora caninum

Abstract Neospora caninum is an apicomplexan parasite that causes abortion in cattle, resulting in significant economic losses. There is no commercial treatment for neosporosis, and drug repositioning is a fast strategy to test possible candidates against N. caninum. In this article, we describe the effects of atovaquone, chloroquine, quinine, primaquine and tetracycline on N. caninum proliferation. The IC50 concentrations in N. caninum were compared to the current information based on previous studies for Plasmodium and Toxoplasma gondii, correlating to the described mechanisms of action of each tested drug. The inhibitory patterns indicate similarities and differences among N. caninum, Plasmodium and T. gondii. For example, atovaquone demonstrates high antiparasitic activity in all the analyzed models, while chloroquine does not inhibit N. caninum. On the other hand, tetracycline is effective against Plasmodium and N. caninum, despite its low activity in T. gondii models. The repurposing of antimalarial drugs in N. caninum is a fast and inexpensive way to develop novel formulations using well-established compounds.

Resumo Neospora caninum é um parasita Apicomplexa relacionado a abortos no gado bovino, que resultam em impactos econômicos. Não há tratamento comercial para neosporosis e o reposicionamento de drogas indica uma estratégia rápida para testar candidatos anti-N. caninum. Neste artigo, são descritos os efeitos da atovaquona, cloroquina, quinino, primaquine e tetraciclina na proliferação de N. caninum. As concentrações IC50 em N. caninum foram comparadas com a informação disponível, baseada em estudos publicados previamente para Plasmodium e Toxoplasma gondii, incluindo a correlação com os mecanismos de ação descritos para cada droga testada. Os padrões de inibição indicam pontos de similaridades e diferenças entre N. caninum, Plasmodium e T. gondii. Por exemplo, a atovaquona demonstra uma alta atividade antiparasitária em todos os modelos testados, enquanto a cloroquina não inibe N. caninum. Por outro lado, a tetraciclina é efetiva contra Plasmodium e N. caninum, em contraste com a baixa atividade em modelos de T. gondii. O reposicionamento de drogas antimaláricas em N. caninum é uma forma rápida e de baixo custo para o desenvolvimento de novas formulações que usam compostos bem estabelecidos.

Partial characterization of Plasmodium falciparum trophozoite proteome under treatment with quinine, mefloquine and the natural antiplasmodial diosgenone / Caracterización parcial del proteoma del trofozoíto de Plasmodium falciparum bajo tratamiento con quinina, mefloquina y el compuesto natural diosgenona

Introduction: Despite efforts to control malaria, around 10% of the world population is at risk of acquiring this disease. Plasmodium falciparum accounts for the majority of severe cases and deaths. Malaria control programs have failed due to the therapeutic failure of first-line antimalarials and to parasite resistance. Thus, new and better therapeutic alternatives are required. Proteomic analysis allows determination of protein expression levels under drug pressure, leading to the identification of new therapeutic drug targets and their mechanisms of action. Objective: The aim of this study was to analyze qualitatively the expression of P.falciparum trophozoite proteins (strain ITG2), after exposure to antimalarial drugs, through a proteomic approach. Materials and methods: In vitro cultured synchronized parasites were treated with quinine, mefloquine and the natural antiplasmodial diosgenone. Protein extracts were prepared and analyzed by two-dimensional electrophoresis. The differentially expressed proteins were selected and identified by MALDI-TOF mass spectrometry. Results: The following proteins were identified among those differentially expressed in the parasite in the presence of the drugs tested: enolase (PF10_0155), calcium-binding protein (PF11_0098), chaperonin (PFL0740c), the host cell invasion protein (PF10_0268) and proteins related to redox processes (MAL8P1.17). These findings are consistent with results of previous studies where the parasite was submitted to pressure with other antimalarial drugs. Conclusion: The observed changes in the P. falciparum trophozoite protein profile induced by antimalarial drugs involved proteins mainly related to the general stress response.

Introducción. A pesar de los esfuerzos para controlar la malaria, esta sigue siendo un problema de salud pública. Plasmodium falciparum es responsable de la mayoría de los casos graves y de las muertes. Los programas de control de la malaria han sido cuestionados debido al fracaso del tratamiento y a la resistencia del parásito a los antipalúdicos de primera línea, por lo que se requieren nuevas y mejores alternativas. El análisis proteómico permite identificar y determinar los niveles de expresión de las proteínas bajo la presión de los medicamentos, lo que posibilita la identificación de nuevos blancos terapéuticos y mecanismos de acción. Objetivo. Analizar cualitativamente la expresión diferencial de proteínas del citosol del trofozoíto de P. falciparum bajo tratamiento con quinina, mefloquina y el compuesto natural diosgenona mediante una aproximación proteómica. Materiales y métodos. Se trataron trofozoítos sincronizados y cultivados in vitro de P. falciparum (cepa ITG2) con quinina, mefloquina y el compuesto natural diosgenona. Los extractos proteicos se prepararon y analizaron por electroforesis bidimensional. Las proteínas con aparente expresión diferencial se seleccionaron e identificaron mediante espectrometría de masas MALDI-TOF. Resultados. Se encontraron las siguientes proteínas diferencialmente expresadas en el trofozoíto: la enolasa (PF10_0155), la proteína de unión a calcio (PF11_0098), la chaperonina (PFL0740c), la proteína de invasión a la célula del huésped (PF10_0268) y la proteína relacionada con procesos de reducción y oxidación (redox) (MAL8P1.17). Estos hallazgos son congruentes con resultados previos de estudios en los que el parásito fue presionado con otros medicamentos antipalúdicos. Conclusión. Los cambios observados en el perfil de proteínas del trofozoíto de P. falciparum tratado con antipalúdicos involucraron preferencialmente proteínas relacionadas con la respuesta al estrés general.

Cuantificación de quinina en extractos de Cinchona pubescens y evaluación de la actividad antiplasmodial y citotóxica / Quantification of quinine in extracts from stems Cinchona pubescens and evaluation of antiplasmodial and cytotoxic activity

Plants belonging to the genus Cinchona L. (Rubiaceae), whose active ingredient is quinine, was used for centuries to treat malaria. Plants of this genus are a potential source of new structural templates in the search for new antimalarial candidates. This study aimed to the identification, quantification of quinine and other metabolites present in extracts of different polarity of the stems of Cinchona pubescens Vahl. , oxoquinovic acid isolation, antiplasmodial activity, and measuring its cytotoxic effect. The results show a high activity to antiplasmodial alkaloids extract (IC50 = 2.20 +/- 0.0325 ug/mL), cytotoxicity (CC50 = 80.2 +/- 12.2 ug/mL), and a quinine content of 21.3+/-0.0247 ppm. The compound known as acid antiplasmodial activity oxoquinovic presented in IC50 = 11.3 +/- 0.741 ug/mL, and cytotoxicity CC50 = 72.4 +/- 3.85 ug/mL. These results motivate phytochemical studies in the search for active structural analogues quinine and quinolinic core as a source of new antimalarial agents.

Las plantas pertenecientes al género Cinchona L. (familia Rubiaceae), cuyo principio activo es la quinina, fueron utilizadas durante siglos para tratar la malaria. Este género es una fuente potencial de nuevas plantillas estructurales en la búsqueda de nuevos candidatos antimaláricos. El presente trabajo tuvo como objetivo la identificación y, cuantificación de la quinina y de otros metabolitos presentes en los extractos de diferente polaridad, de los tallos de Cinchona pubescens Vahl. , el aislamiento del ácido oxoquinóvico, la actividad antiplasmodial y, además, la medición de su efecto citotóxico. Los resultados muestran una alta actividad antiplasmodial para el extracto de los alcaloides (IC50 = 2,20 +/- 0,0325 ug/mL), una baja citotoxicidad (CC50 = 80,2 +/- 12,2 ug/mL), y un alto contenido de quinina el cual fue 21,3+/-0,0247 ppm. El compuesto ácido oxoquinóvico presentó una actividad antiplasmodial de IC50 = 11,3 +/- 0.741 ug/mL, y una citotoxicidad de CC50 = 72,4 +/- 3,85 ug/mL. Estos resultados motivan los estudios fitoquímicos en la búsqueda de principios activos y análogos estructurales en diferentes especies de Cinchonas como una fuente de nuevos agentes antimaláricos.

In vitro susceptibility of Plasmodium falciparum Welch field isolates to infusions prepared from Artemisia annua L. cultivated in the Brazilian Amazon

Artemisinin is the active antimalarial compound obtained from the leaves of Artemisia annua L. Artemisinin, and its semi-synthetic derivatives, are the main drugs used to treat multi-drug-resistant Plasmodium falciparum (one of the human malaria parasite species). The in vitro susceptibility of P. falciparum K1 and 3d7 strains and field isolates from the state of Amazonas, Brazil, to A. annua infusions (5 g dry leaves in 1 L of boiling water) and the drug standards chloroquine, quinine and artemisinin were evaluated. The A. annua used was cultivated in three Amazon ecosystems (várzea, terra preta de índio and terra firme) and in the city of Paulínia, state of São Paulo, Brazil. Artemisinin levels in the A. annua leaves used were 0.90-1.13% (m/m). The concentration of artemisinin in the infusions was 40-46 mg/L. Field P. falciparum isolates were resistant to chloroquine and sensitive to quinine and artemisinin. The average 50% inhibition concentration values for A. annua infusions against field isolates were 0.11-0.14 μL/mL (these infusions exhibited artemisinin concentrations of 4.7-5.6 ng/mL) and were active in vitro against P. falciparum due to their artemisinin concentration. No synergistic effect was observed for artemisinin in the infusions.

Drug Resistance and in Vitro Susceptibility of Plasmodium falciparum in Thailand during 1988-2003

The aim of the present study was to investigate antimalarial drug pressure resulting from the clinical use of different antimalarials in Thailand. The phenotypic diversity of the susceptibility profiles of antimalarials, i.e., chloroquine (CQ), quinine (QN), mefloquine (MQ), and artesunate (ARS) in Plasmodium falciparum isolates collected during the period from 1988 to 2003 were studied. P. falciparum isolates from infected patients were collected from the Thai-Cambodian border area at different time periods (1988-1989, 1991-1992, and 2003), during which 3 different patterns of drug use had been implemented: MQ + sulphadoxine (S) + pyrimethamine (P), MQ alone and MQ + ARS, respectively. The in vitro drug susceptibilities were investigated using a method based on the incorporation of [3H] hypoxanthine. A total of 50 isolates were tested for susceptibilities to CQ, QN, MQ, and ARS. Of these isolates, 19, 16, and 15 were adapted during the periods 1988-1989, 1991-1993, and 2003, respectively. P. falciparum isolates collected during the 3 periods were resistant to CQ. Sensitivities to MQ declined from 1988 to 2003. In contrast, the parasite was sensitive to QN, and similar sensitivity profile patterns were observed during the 3 time periods. There was a significantly positive but weak correlation between the IC50 values of CQ and QN, as well as between the IC50 values of QN and MQ. Drug pressure has impact on sensitivity of P. falciparum to MQ. A combination therapy of MQ and ARS is being applied to reduce the parasite resistance, and also increasing the efficacy of the drug.

In vitro antimalarial activity of methylene blue against field isolates of Plasmodium falciparum from children in Southwest Nigeria.

BACKGROUND & OBJECTIVES: Methylene blue (MB), a thiazine dye is used in the treatment of various methemoglobinaemias. However, sporadic reports have shown some antimalarial therapeutic effect when administered to patients with clinical manifestations of malaria. The inhibitory concentration of schizont maturation and antimalarial activity of MB have not been fully elucidated. The present study therefore aimed at determining the antimalarial activity of MB in Plasmodium falciparum isolates obtained from children with malaria using standard in vitro drug susceptibility test. METHODS: Twenty children (8 boys and 12 girls) within the age range 4.5-11.5 yr were enrolled into the study and 2 ml of blood withdrawn aseptically. The standard microtest technique of schizont inhibition assay was used to culture fresh isolates obtained from P. falciparum infected patients. Chloroquine (CQ) and quinine (QN) were used as reference standards for in vitro drug susceptibility tests. RESULTS: The mean 50 per cent inhibitory concentration (IC(50)) values were 9.59 +/- 3.25nM, 196 +/-21.11nM and 607 +/- 27.41nM for MB, CQ and QN respectively. Ten of the 14 isolates were sensitiveto MB, 11 were sensitive to CQ while nine were sensitive to QN. Three isolates were resistant to CQ,and of these, two were sensitive to MB and one was sensitive to QN. INTERPRETATION & CONCLUSION: This preliminary study showed that MB has high antimalarial activity comparable with CQ and QN and may be used as a potent schizonticidal drug against CQ-resistant isolates.

In vitro study assessing the response of plasmodium falciparum malaria to chloroquine, sulfadoxine/pyrimethamine, quinine and mefloquine in Wad Medani district, Sudan

To assess the in vitro response of Plasmodium falciparum malaria to chloroquine [CQ], sulfadoxine/pyrimethamine [SDX/PYR], Quinine [QU] and Mefloquine [MQ] and monitoring their resistance. In 1999 to 2000, an in vitro study was carried out in Wad Medani district in Sudan. The standard protocol of the WHO in vitro micro-test Mark II was used for the selection of the subjects, the collection of blood samples, the culture techniques, the examination of the post-culture blood slides and the interpretation of the results. In vitro micro-test Mark II were performed on 62 Plasmodium falciparum isolates. Of these isolates, 42 produced successful schizonts growth. The data obtained showed that 29 of 42 isolates [69%] were CQ resistant with an effective concentrations [EC]; EC50 = 399.621 nM, EC90 = 2754.145 nM and EC99 = 13284.967 nM to inhibit the schizont maturation, the values of SDX/PYR showed a flat regression line as an indication of in vitro reduced response with an EC50 = 0.262 nM, EC90 = 147.390 nM and EC99 = 25722.296 nM, and the response to the QU indicated only one of the 42 isolates [2.4%] was resistant with an EC50 = 150.085 nM, EC90 = 822.825 nM and EC99 = 3293.667 nM, while all the 42 isolates were sensitive to MQ with an EC50 = 190.763 nM, EC90 = 615.125 nM and EC99 = 1597.504 nM. The results of this study revealed a high degree of in vitro resistance to CQ and reduced in vitro response to SDX/PYR and QU, while MQ was fully sensitive. The effective concentrations to inhibit 50, 90 and 99% of the parasite maturation were determined for antimalarial drugs efficacy monitoring surveillance in Sudan

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

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 mumol/L of blood while IC50 from 0.053 to 8.132 mumol/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

Lack of efficacy of quinine and artemether against advanced third-stage larvae of Gnathostoma spinigerum in vitro.

The efficacy of quinine and artemether--the effective blood schizontocide in malarial treatment--has been in vitro tested with the advanced third-stage larvae of Gnathostoma spinigerum. All larvae were collected from freshwater eel (Fluta alba) and exposed to the culture medium, each containing either quinine dihydrochloride or artemether at a final concentration of 20 microg/ml and 0.5 microg/ml, respectively for 21 consecutive days. Larval motility was assessed daily and the topographical changes were assessed using scanning electron microscope after 21-days of drug exposure. All worms moved actively for 21 days of study period and no change in surface ultrastructure was observed. Quinine and artemether at these concentrations have no effect on movement and topographical changes on the advanced third-stage larvae of this parasite.

Malária por Plasmodium falciparum: análise quadrienal, durante 12 anos, da eficácia do tramento com quinino / Falciparum malaria: quadrennial analysis, during 12 years of the quinine treatment eficacy

A eficácia do quinino no tratamento da malária por P. falciparum foi estudada mediante análise quadrienal de 454 prontuários de pacientes internados no HDT-GO. de 1983 a 1994, tratados somente com quinino na mesma dosagem, durante 7 dias. No quadriênio de 1983 a 1986, 98.4 por cento dos pacientes tratados näo apresentavam parasitemia assexuada já no 5§ dia de tratamento e o índice de recrudescência tardia (Rû) foi 8 por cento, de 1987 a 1990, apenas 72,9 por cento estavam sem parasitemia no 5§ dia, 1,4 por cento continuavam com parasitemia no 7§ dia (R2) e o índice de recrudescência (R1) foi 17 por cento; de 1991 a 1994, 70,3 por cento estavam sem parasitemia no 5§ dia, 3,5 por cento continuavam com parasitemia no 7§ dia (R2) e o índice de recrudescência (R1) foi 20 por cento. O aumento gradual na persistência da parasitemia, inclusive até o 7§ dia de tratamento (R2)e da recrudescência tardia (R1), indicam estar o P. falciparum desenvolvendo, na área do estudo, resistência ao quinino

The effects of quinine and artesunate treatment on plasma tumor necrosis factor levels in malaria-infected patients.

Tumor necrosis factor-alpha (TNF-alpha) is an endogenous mediator of shock and inflammation including malaria. Many lines of evidence suggest that cytoadherence, the life-threatening pathology associated with complicated and cerebral malaria, results from the overproduction of TNF in response to malarial parasite. Quinine has been shown to inhibit TNF synthesis and cytoadherence in vitro suggesting an additional beneficial effect of quinine on its anti-TNF action. On the other hand, artesunate inhibits cytoadherence better than quinine does not suppress TNF production in vitro. The present study compares the effect of artesunate and quinine on TNF levels of malaria-infected patients. Surprisingly, plasma TNF levels increased dramatically after quinine administration but did not increase after artesunate administration. This difference may be explained by previous observations showing that artesunate kills parasites in vitro and clears parasitemias in vivo for more rapidly than quinine. The rapid clearance of plasma TNF in quinine treated patients might be due to the drug's TNF-suppressive activity.

In vitro sensitivity of Plasmodium falciparum to eight antimalarials in China-Myanmar and China-Lao PDR border areas.

In 1991-1995 by using the Rieckmann in vitro micro-method, susceptibilities of Plasmodium falciparum to eight antimalarials in the China-Lao PDR and China-Myanmar border areas were tested. The resistant rates of P. falciparum to chloroquinine were 95.0%-100%; IC50 114-240nmol/l. P. falciparum resistant rates to amodiaquine resistance accounted for 83.5%-100%, IC50 52-72nmol/l. All cases were sensitive to quinine, IC50 470-608nmol/l. P. falciparum isolates from the Lao PDR frontier were highly sensitive to artesunate, dihydroartemisinin, and arteether. Resistant rates from other areas were 0-11%. P. falciparum from China-Myanmar and Lao PDR border areas were also sensitive to mefloquine, IC50 68-88nmol/l. A longitudinal survey of the sensitivity of P. falciparum in vivo on the China-Lao PDR border showed that the average defervescent time of falciparum malaria was treated by pyronaridine increased from 32.7 +/- 16.0 hours during 1984-85 to 56.2 +/- 27.4 hours in 1995; the recrudescence rate rose up from 15.2% to 37.5%. The results monitored in vitro showed that all cases assessed in 1988 for response to pyronaridine were sensitive, but 36.4% of cases had emerging resistance, IC50 increased from 13nmol/l to 40 nmol/l. The above results suggested that P. falciparum in these areas has expressed resistance to chloroquine and amodiaquine. However, the parasites are still sensitive to artemisinin, pyronaridine, mefloquine, quinine, but with a declining sensitivities.

Study on modification of hypoglycaemic effect of quinine by doxycycline in albino rats.

Hypoglycemia has been reported to occur in the patients and animals infected with various species of plasmodium (1). The use of quinine has been associated with significant decrease in blood sugar level, thus worsening the prognosis (2). In such a situation cautious thinking of possible drug interaction which may, further, aggravate the hypoglycemia is mandatory. But the data of the drug interaction of the combination of quinine and doxycycline in the treatment of chloroquine or multi-drug resistant falciparum malaria are not available. This study was aimed to find out whether this combination can cause more hypoglycemia when compared to quinine alone.

Taste disorder in hypo and hyperthyroidism.

Gustatory responses to the basic taste substances (sweet, salty, sour and bitter) were studied in hypothyroid and hyperthyroid subjects. The intensity and hedonic responses were evaluated using "category scaling" for 7 concentrations of glucose, sodium chloride, citric acid and quinine sulphate. The intensity and hedonic values decrease in hyperthyroidism for salt and bitter solution, and sourness is perceived as more unpleasant. In hypothyroid subjects intensity and hedonic value decreases for sweetness, the pleasant responses to salt and bitter increase, though intensity perception decreases for bitter solutions.

An in vitro study on mefloquine/quinine in Plasmodium falciparum malaria.

An in vitro designed for determining sensitivity of Plasmodium falciparum strains isolated from Kanchanaburi Province, to Mefloquine/Quinine combination, was carried out. The MIC values of Mefloquine/Quinine for the P.falciparum strains were found to be 0.075/3.75 to 0.225/11.15 nM/ml. The changes observed following the drug treatment were an enlargement of the space between the outer and the inner limiting membrane of the parasitophorous vacuole. These changes were followed by cytoplasmic degeneration and vacuolation.

Quinine resistant falciparum malaria treated with mefloquine.

Twenty eight adult male patients with acute uncomplicated falciparum malaria which showed RI or RII responses to quinine sulfate at the dosage of 600 mg 8 hourly for 7, 10 or 14 days were treated with a single dose of mefloquine (Lariam); 25 patients received 1000 mg, 2 received 750 mg and 1 received 500 mg. The initial response was good; there was no RII or RIII response. Three patients were lost to followup. Of 25 patients who stayed in the Bangkok Hospital for Tropical Diseases where there was no malaria transmission for 28-65 days, only one patient in the 1000 mg group had recrudescence on day 21. The cure rate was 96%. Our prospective study suggests that mefloquine was effective in the treatment of quinine resistant falciparum malaria and the risk of cross-resistance between quinine and mefloquine in P. falciparum in vivo is very low.

Gustatory differences in hypothyroid and hyperthyroid tasters and non-tasters.

Gustatory differences in Phenylthiocarbamide (PTC) tasters and non-tasters were studied in hypothyroid and hyperthyroid subjects. After presenting for PTC sensitivity, gustatory responses to 7 dilutions of test solutions for glucose (sweet), sodium chloride (salt), citric acid (sour) and quinine sulphate (bitter) were studied in PTC tasters and non-tasters. The intensity and pleasantness responses for 4 basic tastes were measured on a 7-point and 6-point category scale respectively. Sixty percent of subjects of hyperthyroid and 40% of hypothyroid subjects were tasters. Hypothyroid subjects showed more gustatory differences as compared to hyperthyroids. The diminished intensity perception for sweet and bitter taste was much more prominent in non-tasters than tasters hypothyroids. The greater hedonic value for salt was largely observed among hypothyroid tasters.

Incidence of P.T.C. taste sensitivity and threshold in Kashmiri population.

Taste sensitivity and threshold of Phenylthiourea (PTC) was determined in 800 individuals of Kashmir who form a distinct ethnic group. Correlation, if any, with age, sex, blood group, pH of Saliva, or smoking habits was investigated. The taste sensitivity of P.T.C. increased with advancing age. The percentage of non-tasters was more in blood group 'B' & 'O'. However, no correlation was observed as far as sex, pH of saliva and smoking habits were concerned.

Estudos "in vitro" dos níveis de resistência do Plasmodium falciparum a drogas, de 1983 a 1986 / In vitro studies of the levels of resistance to drugs of Plasmodium falciparum, from 1983 to 1986

Foram realizados 171 testes de sensibilidade (microtécnica) com cepas de Plasmodium falciparum da Regiäo Amazónica brasileira para cloroquina, mefloquina, amodiaquina e quinino. Os testes tiveram duraçäo de 24 horas com as drogas preparadas na hora de realizaçäo de cada teste. Os resultados mostraram elevada resistência a cloroquina (83%) e sensibilidade em quase a totalidade das amostras testadas para mefloquina (97,7%). Para amodiaquina e quinino observou-se sensibilidade em 51,0% e 56,5% das cepas, respectivamente. Este estudo demonstra a emergência de um possível foco de resistência do Plasmodium falciparum a mefloquina, em Tucuruí