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1.
Rev. Soc. Bras. Med. Trop ; 54: e05362020, 2021. tab, graf
Article in English | LILACS | ID: biblio-1155593

ABSTRACT

Abstract INTRODUCTION: Artemisinin-based combination therapy (ACT), such as artemisinin-piperaquine (AP), dihydroartemisinin-piperaquine (DP), and artemether-lumefantrine (AL), is the first-line treatment for malaria in many malaria-endemic areas. However, we lack a detailed evaluation of the cardiotoxicity of these ACTs. This study aimed to analyze the electrocardiographic effects of these three ACTs in malaria patients. METHODS: We analyzed the clinical data of 89 hospitalized patients with falciparum malaria who had received oral doses of three different ACTs. According to the ACTs administered, these patients were divided into three treatment groups: 27 treated with AP (Artequick), 31 with DP (Artekin), and 31 with AL (Coartem). Electrocardiograms and other indicators were recorded before and after the treatment. The QT interval was calculated using Fridericia's formula (QTcF) and Bazett's formula (QTcB). RESULTS: Both QTcF and QTcB interval prolongation occurred in all three groups. The incidence of such prolongation between the three groups was not significantly different. The incidence of both moderate and severe prolongation was not significantly different between the three groups. The ΔQTcF and ΔQTcB of the three groups were not significantly different. The intra-group comparison showed significant prolongation of QTcF after AL treatment. CONCLUSIONS: Clinically recommended doses of DP, AL, and AP may cause QT prolongation in some malaria patients but do not cause torsades de pointes ventricular tachycardia or other arrhythmias.


Subject(s)
Humans , Malaria, Falciparum/drug therapy , Artemisinins/adverse effects , Malaria/drug therapy , Antimalarials/adverse effects , Quinolines , Drug Combinations , Electrocardiography , Artemether/therapeutic use , Artemether, Lumefantrine Drug Combination/therapeutic use
2.
Rev. Soc. Bras. Med. Trop ; 52: e20180453, 2019. tab, graf
Article in English | LILACS | ID: biblio-1041531

ABSTRACT

Abstract INTRODUCTION: Concern regarding the cardiotoxicity of antimalarials has been renewed because of their potential to cause QT/QTc interval prolongation related to torsade de pointes (TdP). Artemisinin-piperaquine (AP) is considered an effective artemisinin-based combination therapy (ACT) for malaria. METHODS: This study involved a retrospective analysis of clinical data of 93 hospitalized malaria patients who had received AP orally. Electrocardiograms (ECGs) were obtained at specific time points in the original study. RESULTS: Some cases of QT prolongation were observed. However, no TdP was found. CONCLUSIONS: AP may cause QT interval prolongation in some malaria patients but may not lead to TdP.


Subject(s)
Humans , Male , Female , Adult , Quinolines/adverse effects , Long QT Syndrome/chemically induced , Malaria, Falciparum/drug therapy , Artemisinins/adverse effects , Antimalarials/adverse effects , Quinolines/therapeutic use , Long QT Syndrome/diagnosis , Retrospective Studies , Artemisinins/therapeutic use , Drug Therapy, Combination , Electrocardiography , Middle Aged , Antimalarials/therapeutic use
3.
Rev. Soc. Bras. Med. Trop ; 52: e20190163, 2019.
Article in English | LILACS | ID: biblio-1041528

ABSTRACT

Abstract Artemisinin-based combination therapy (ACT) is recommended by the World Health Organization for the treatment of uncomplicated malaria. Currently, there appears to be a downward trend in the efficacy of ACT in some parts of sub-Saharan Africa because some patients have been positive for Plasmodium parasite 3 days after artemether-lumefantrine treatment. We reported three cases of possible parasite resistance to artemether-lumefantrine therapy. All subjects had complete parasite clearance when treated with other antimalarial drugs. This observation necessitates the urgent need to re-evaluate artemether-lumefantrine medication in Nigeria since it is one of the most commonly used ACT drug.


Subject(s)
Humans , Male , Female , Adult , Young Adult , Malaria, Falciparum/drug therapy , Artemether, Lumefantrine Drug Combination/therapeutic use , Antimalarials/therapeutic use , Treatment Failure , Artemether, Lumefantrine Drug Combination/adverse effects , Middle Aged , Antimalarials/adverse effects
4.
Braz. j. infect. dis ; 20(5): 482-486, Sept.-Oct. 2016. tab, graf
Article in English | LILACS | ID: biblio-828133

ABSTRACT

Abstract Objective To evaluate whether patient age has a significant impact on mefloquine concentrations in the plasma and erythrocytes over the course of treatment for uncomplicated falciparum malaria. Methods A total of 20 children aged between 8 and 11 years and 20 adult males aged between 22 and 41 years with uncomplicated falciparum malaria were enrolled in the study. Mefloquine was administered to patients in both age groups at a dose of 20 mg kg−1. The steady-state drug concentrations were measured by reversed-phase high performance liquid chromatography. Results All patients had an undetectable mefloquine concentration on day 0. In adults, the plasma mefloquine concentrations ranged from 770 to 2930 ng mL−1 and the erythrocyte concentrations ranged from 2000 to 6030 ng mL−1. In children, plasma mefloquine concentrations ranged from 881 to 3300 ng mL−1 and erythrocyte concentrations ranged from 3000 to 4920 ng mL−1. There was no significant correlation between mefloquine concentrations in the plasma and erythrocytes in either adults or children. Conclusion In the present study, we observed no effect of patient age on the steady-state concentrations of mefloquine in the plasma and erythrocytes. We found that the mefloquine concentration in the erythrocytes was approximately 2.8-times higher than in the plasma. There were no significant correlations between mefloquine concentrations in the erythrocytes and plasma for either age group.


Subject(s)
Humans , Male , Child , Adult , Young Adult , Mefloquine/blood , Age Factors , Malaria, Falciparum/drug therapy , Malaria, Falciparum/blood , Antimalarials/blood , Plasma , Reference Values , Time Factors , Acute Disease , Statistics, Nonparametric , Erythrocytes/drug effects , Chromatography, Reverse-Phase
6.
Article in English | LILACS | ID: lil-758425

ABSTRACT

The preoccupation to find new drugs for the treatment of malaria is increasing steadily due to the resistance of the parasite, which is a threat to disease control, The present study describes a literature review on the antimalarial ethnopharmacology (Anti-Plasmodium falciparum - in vitro) of the Brazilian Amazon plants, It was found a great diversity of plant species in the Brazilian Amazon with potential for research of new herbal and secondary metabolites with antiplasmodial action, in addition to treating other neglected parasitic diseases, However, for these studies is needed in addition to financial support, the interaction between different laboratories and research groups for the formation of multidisciplinary and interdisciplinary teams, which will enhance the research level in the region and increase the likelihood of new antimalarial drugs discovery...


Está cada vez maior a necessidade em se buscar novos fármacos para o tratamento da malária, principalmente devido à resistência do parasito, o que é uma ameaça ao controle da doença. O presente estudo descreve uma revisão bibliográfica sobre a etnofarmacologia antimalárica (Anti-Plasmodium falciparum - in vitro) de plantas da Amazônia brasileira. Constatou-se uma grande diversidade de espécies vegetais na Amazônia brasileira com potencial para a investigação de novos fitoterápicos e metabólitos secundários com ação antiplasmodial, além do tratamento de outras parasitoses negligenciadas. Porém, para a realização desses estudos são necessários além de apoio financeiro, a interação entre diferentes laboratórios e grupos de pesquisa para a formação de equipes multidisciplinares e interdisciplinares, o que irá potencializar o nível da pesquisa na região e aumentar a probabilidade de descoberta de novos fármacos antimaláricos...


Subject(s)
Humans , Antimalarials/pharmacology , Ethnopharmacology/trends , Malaria, Falciparum/drug therapy , Brazil , Drug Resistance
7.
Article in English | WPRIM | ID: wpr-225155

ABSTRACT

The parasite Plasmodium falciparum causes severe malaria and is the most dangerous to humans. However, it exhibits resistance to their drugs. Farnesyltransferase has been identified in pathogenic protozoa of the genera Plasmodium and the target of farnesyltransferase includes Ras family. Therefore, the inhibition of farnesyltransferase has been suggested as a new strategy for the treatment of malaria. However, the exact functional mechanism of this agent is still unknown. In addition, the effect of farnesyltransferase inhibitor (FTIs) on mitochondrial level of malaria parasites is not fully understood. In this study, therefore, the effect of a FTI R115777 on the function of mitochondria of P. falciparum was investigated experimentally. As a result, FTI R115777 was found to suppress the infection rate of malaria parasites under in vitro condition. It also reduces the copy number of mtDNA-encoded cytochrome c oxidase III. In addition, the mitochondrial membrane potential (DeltaPsim) and the green fluorescence intensity of MitoTracker were decreased by FTI R115777. Chloroquine and atovaquone were measured by the mtDNA copy number as mitochondrial non-specific or specific inhibitor, respectively. Chloroquine did not affect the copy number of mtDNA-encoded cytochrome c oxidase III, while atovaquone induced to change the mtDNA copy number. These results suggest that FTI R115777 has strong influence on the mitochondrial function of P. falciparum. It may have therapeutic potential for malaria by targeting the mitochondria of parasites.


Subject(s)
Antimalarials/pharmacology , Enzyme Inhibitors/pharmacology , Farnesyltranstransferase/antagonists & inhibitors , Humans , Malaria, Falciparum/drug therapy , Mitochondria/drug effects , Plasmodium falciparum/drug effects , Protozoan Proteins/antagonists & inhibitors , Quinolones/pharmacology
8.
Belo Horizonte; s.n; 2015. 113 p.
Thesis in Portuguese | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-941615

ABSTRACT

A resistência de Plasmodium falciparum aos antimaláricos esquizonticidas sanguíneos disponíveis, como a atovaquona e derivados de artemisinina, e a de P. vivax à cloroquina (CQ), exige a busca por alternativas quimioterápicas, objetivo deste trabalho. Como estratégia geradora de novos protótipos antimaláricos, foram feitas modificações estruturais (i) na CQ, as quais resultaram em 10 análogos de cloroquina (AnCQ), sendo quatro complexados com platina (AnCQPt), com atividade previamente descrita na malária pelo P. berghei; (ii) na atovaquona, originando oito naftoquinonas; e (iii) no lapachol, resultando em 11 compostos naftoquinoidais. Essas classes de moléculas foram avaliadas in vitro quanto a sua citotoxicidade (MCL50) e atividade antiplasmodial (IC50) contra parasitos sensíveis(S) ou resistentes(R) à CQ. Os índices de seletividade (IS), expressos pela razão entre essas duas atividades biológicas, foram obtidos. Os AnCQ foram mais ativos contra P. falciparum CQ-R in vitro e mais ativos que os AnCQPt e mostraram IS superiores ao da CQ. Para elucidar seu modo de ação, os AnCQ foram avaliados in silico quanto à ancoragem molecular na lactato-desidrogenase de P. falciparum(PfLDH) ou humana (HssLDH).


O AnCQ33 apresentou melhor conformação na PfLDH; AnCQ37 apresentou especificidade em relação à enzima humana. Os AnCQ com maiores IS (AnCQ 33 e 37) e a CQ foram ainda avaliados quanto sua capacidade de inibir a formação de Beta-hematina, sendo tão ou menos ativos que a CQ. Avaliados quanto ao potencial de causar a morte (atividade citocida) ou impedir o crescimento (atividade citostática) de P. falciparum CQ-Se CQ-R, esses análogos demonstraram potencial citocida similar, e potencial citostático maior contra parasitos CQ-R. Os AnCQ foram ativos contra parasitos CQ-S e CQ-R na malária pelo P. berghei. Duas naftoquinonas (2 e 5) apresentaram IS superiores ao da CQ e inibiram a parasitemia pelo P. bergheiem camundongos, com destaque para a naftoquinona 2. Em conclusão, os melhores candidatos à produção de um antimalárico esquizonticida sanguíneo foram AnCQ33 e 37 e a naftoquinona 2.


Subject(s)
Male , Female , Humans , Antimalarials/therapeutic use , Chloroquine/therapeutic use , Malaria, Falciparum/drug therapy , Plasmodium falciparum/parasitology
9.
Belo Horizonte; s.n; 2015. 113 p.
Thesis in Portuguese | LILACS | ID: lil-766610

ABSTRACT

A resistência de Plasmodium falciparum aos antimaláricos esquizonticidas sanguíneos disponíveis, como a atovaquona e derivados de artemisinina, e a de P. vivax à cloroquina (CQ), exige a busca por alternativas quimioterápicas, objetivo deste trabalho. Como estratégia geradora de novos protótipos antimaláricos, foram feitas modificações estruturais (i) na CQ, as quais resultaram em 10 análogos de cloroquina (AnCQ), sendo quatro complexados com platina (AnCQPt), com atividade previamente descrita na malária pelo P. berghei; (ii) na atovaquona, originando oito naftoquinonas; e (iii) no lapachol, resultando em 11 compostos naftoquinoidais. Essas classes de moléculas foram avaliadas in vitro quanto a sua citotoxicidade (MCL50) e atividade antiplasmodial (IC50) contra parasitos sensíveis(S) ou resistentes(R) à CQ. Os índices de seletividade (IS), expressos pela razão entre essas duas atividades biológicas, foram obtidos. Os AnCQ foram mais ativos contra P. falciparum CQ-R in vitro e mais ativos que os AnCQPt e mostraram IS superiores ao da CQ. Para elucidar seu modo de ação, os AnCQ foram avaliados in silico quanto à ancoragem molecular na lactato-desidrogenase de P. falciparum(PfLDH) ou humana (HssLDH)...


Subject(s)
Humans , Male , Female , Antimalarials/therapeutic use , Chloroquine/therapeutic use , Malaria, Falciparum/drug therapy , Plasmodium falciparum/parasitology
10.
Article in English | WPRIM | ID: wpr-130572

ABSTRACT

Pyronaridine and artesunate have been shown to be effective in falciparum malaria treatment. However, pyronaridine is rarely used in Hainan Island clinically, and artesunate is not widely used as a therapeutic agent. Instead, conventional antimalarial drugs, chloroquine and piperaquine, are used, explaining the emergence of chloroquine-resistant Plasmodium falciparum. In this article, we investigated the sensitivity of P. falciparum to antimalarial drugs used in Hainan Island for rational drug therapy. We performed in vivo (28 days) and in vitro tests to determine the sensitivity of P. falciparum to antimalarial drugs. Total 46 patients with falciparum malaria were treated with dihydroartemisinin/piperaquine phosphate (DUO-COTECXIN) and followed up for 28 day. The cure rate was 97.8%. The mean fever clearance time (22.5+/-10.6 hr) and the mean parasite clearance time (27.3+/-12.2 hr) showed no statistical significance with different genders, ages, temperatures, or parasite density (P>0.05). The resistance rates of chloroquine, piperaquine, pyronarididine, and artesunate detected in vitro were 71.9%, 40.6%, 12.5%, and 0%, respectively (Ppiperaquine>pyronarididine>artesunate. The inhibitory dose 50 (IC50) was 3.77x10(-6) mol/L, 2.09x10(-6) mol/L, 0.09x10(-6) mol/L, and 0.05x10(-6) mol/L, and the mean concentrations for complete inhibition (CIMC) of schizont formation were 5.60x10(-6) mol/L, 9.26x10(-6) mol/L, 0.55x10(-6) mol/L, and 0.07x10(-6) mol/L, respectively. Dihydroartemisinin showed a strong therapeutic effect against falciparum malaria with a low toxicity.


Subject(s)
Adolescent , Adult , Aged , Antimalarials/pharmacology , Child , Child, Preschool , China , Female , Humans , Inhibitory Concentration 50 , Malaria, Falciparum/drug therapy , Male , Middle Aged , Parasitic Sensitivity Tests , Plasmodium falciparum/drug effects , Treatment Outcome , Young Adult
11.
Article in English | WPRIM | ID: wpr-130565

ABSTRACT

Pyronaridine and artesunate have been shown to be effective in falciparum malaria treatment. However, pyronaridine is rarely used in Hainan Island clinically, and artesunate is not widely used as a therapeutic agent. Instead, conventional antimalarial drugs, chloroquine and piperaquine, are used, explaining the emergence of chloroquine-resistant Plasmodium falciparum. In this article, we investigated the sensitivity of P. falciparum to antimalarial drugs used in Hainan Island for rational drug therapy. We performed in vivo (28 days) and in vitro tests to determine the sensitivity of P. falciparum to antimalarial drugs. Total 46 patients with falciparum malaria were treated with dihydroartemisinin/piperaquine phosphate (DUO-COTECXIN) and followed up for 28 day. The cure rate was 97.8%. The mean fever clearance time (22.5+/-10.6 hr) and the mean parasite clearance time (27.3+/-12.2 hr) showed no statistical significance with different genders, ages, temperatures, or parasite density (P>0.05). The resistance rates of chloroquine, piperaquine, pyronarididine, and artesunate detected in vitro were 71.9%, 40.6%, 12.5%, and 0%, respectively (Ppiperaquine>pyronarididine>artesunate. The inhibitory dose 50 (IC50) was 3.77x10(-6) mol/L, 2.09x10(-6) mol/L, 0.09x10(-6) mol/L, and 0.05x10(-6) mol/L, and the mean concentrations for complete inhibition (CIMC) of schizont formation were 5.60x10(-6) mol/L, 9.26x10(-6) mol/L, 0.55x10(-6) mol/L, and 0.07x10(-6) mol/L, respectively. Dihydroartemisinin showed a strong therapeutic effect against falciparum malaria with a low toxicity.


Subject(s)
Adolescent , Adult , Aged , Antimalarials/pharmacology , Child , Child, Preschool , China , Female , Humans , Inhibitory Concentration 50 , Malaria, Falciparum/drug therapy , Male , Middle Aged , Parasitic Sensitivity Tests , Plasmodium falciparum/drug effects , Treatment Outcome , Young Adult
12.
European J Med Plants ; 2014 Dec; 4(12): 1378-1387
Article in English | IMSEAR | ID: sea-164204

ABSTRACT

Aim: Antiplasmodial potential of traditional medicinal plant Thlaspi arvense against Plasmodium falciparum in vitro has been evaluated. Cytotoxicity of plant extract against HeLa cell lines and normal fibroblasts has also been observed. Place and Duration of the Study: Department of Zoology, Panjab University, Chandigarh, India, between May 2013 to April 2014. Materials and Methods: Ethanolic whole plant extract of Thlaspi arvense (EWETA) was analyzed for its phytochemical constituents. In vitro cytotoxicity was determined colorimetrically by MTT assay. WHO protocol, based on assessment of schizont maturation inhibition, was employed for the evaluation of in vitro antiplasmodial activity of plant extract. Results: Phytochemical screening of EWETA revealed the presence of diterpenes, triterpenes, steroids, anthraquinones and phytosterols. EWETA was observed to inhibit schizont maturation of both chloroquine-sensitive (MRC-2) and resistant (RKL-9) strains of P. falciparum with IC50<5μg/ml and =5μg/ml respectively. The extract was revealed to be safe against both HeLa cells and normal fibroblasts with CC50>1000μg/ml. Selectivity index for Thlaspi arvense was calculated to be >200 and =200 both for chloroquine sensitive and chloroquine-resistant strains of P. falciparum with both HeLa and normal fibroblasts. Conclusion: Plant extract possesses considerable in vitro antimalarial activity with high selectivity index (SI>10) pointing field pennycress to be an active antimalarial. Hence, present study provides scientific evidence for traditional usage of the plant as an antipyretic agent.


Subject(s)
Antimalarials/pharmacology , Humans , India , Malaria, Falciparum/drug therapy , Medicine, Traditional , Microbial Sensitivity Tests , Microbial Viability/drug effects , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/toxicity , Plasmodium falciparum/drug effects , Thlaspi
13.
Rev. chil. infectol ; 31(5): 549-554, oct. 2014. graf, tab
Article in Spanish | LILACS | ID: lil-730271

ABSTRACT

Introduction: During malaria infection, both parasite and host are under the effects of oxidative stress due to the increased production of reactive oxygen species, which can induce DNA damage by its genotoxic effects. Objective: To evaluate genotoxic effects in human lymphocytes in a cohort of patients with malaria from Medellin and Quibdó. Methods: We performed an observational cross sectional study in 100 individuals with malaria and 100 healthy controls. Patients infected with Plasmodium consulting the Institute Colombiano of Medicina Tropical of Medellin and the Hospital Ismael Roldán Valencia of Quibdó were included. Genotoxic effects (genetic damage) was analysed by electrophoresis using alkaline single cell gel (Commet assay). Results: The average of tail length of malaria samples (26.9 ± 9.8) was significantly higher than of controls (14.8 ± 3.2) (p < 0.01). Conclusion: In our study population, malaria infection was associated with increased genotoxicity, while other variables such as smoking, antimalarial treatment, and occupation were not.


Introducción: Durante la infección de la malaria, tanto el parásito como el hospedero están bajo los efectos de estrés oxidativo, dado que se aumenta la producción de especies reactivas del oxígeno, las cuales pueden inducir daños en el ADN debido a su gran efecto genotóxico. Objetivo: Evaluar el efecto genotóxico en linfocitos humanos en una cohorte de pacientes con malaria de Medellín y Quibdó. Métodos: Se realizó un estudio observacional transversal en 100 personas con malaria y 100 controles sanos. Se incluyeron pacientes infectados con Plasmodium, que consultaron en el Instituto Colombiano de Medicina Tropical de Medellín y el Hospital Ismael Roldán Valencia de Quibdó. Se realizó una valoración transversal del efecto (daño genético) mediante electro-foresis en gel de células individuales (ensayo Cometa). Resultados: El promedio de longitud de la cola de los pacientes (26,9 ± 9,8) fue significativamente mayor que la media de los controles sanos (14,8 ± 3,2) (p < 0,01). Conclusión: Se evidenció en la población de estudio que la infección por malaria generó genotoxicidad, no así variables como tabaquismo, tratamiento antimalárico y ocupación.


Subject(s)
Female , Humans , Male , DNA Damage/genetics , Lymphocytes/parasitology , Malaria, Falciparum/genetics , Malaria, Vivax/genetics , Oxidative Stress/genetics , Case-Control Studies , Colombia , Cross-Sectional Studies , Malaria, Falciparum/drug therapy , Malaria, Vivax/drug therapy , Plasmodium falciparum , Plasmodium vivax , Risk Factors , Smoking
14.
Article in English | WPRIM | ID: wpr-229074

ABSTRACT

Genetic characteristics of Plasmodium falciparum may play a role in the treatment outcome of malaria infection. We have studied the association between diversity at the merozoite surface protein-1 (msp-1), msp-2, and glutamate-rich protein (glurp) loci and the treatment outcome of uncomplicated falciparum malaria patients along the Thai-Myanmar border who were treated with artemisinin derivatives combination therapy. P. falciparum isolates were collected prior to treatment from 3 groups of patients; 50 cases of treatment failures, 50 recrudescences, and 56 successful treatments. Genotyping of the 3 polymorphic markers was analyzed by nested PCR. The distribution of msp-1 alleles was significantly different among the 3 groups of patients but not the msp-2 and glurp alleles. The allelic frequencies of K1 and MAD20 alleles of msp1 gene were higher while RO33 allele was significantly lower in the successful treatment group. Treatment failure samples had a higher median number of alleles as compared to the successful treatment group. Specific genotypes of msp-1, msp-2, and glurp were significantly associated with the treatment outcomes. Three allelic size variants were significantly higher among the isolates from the treatment failure groups, i.e., K1270-290, 3D7610-630, G650-690, while 2 variants, K1150-170, and 3D7670-690 were significantly lower. In conclusion, the present study reports the differences in multiplicity of infection and distribution of specific alleles of msp-1, msp-2, and glurp genes in P. falciparum isolates obtained from treatment failure and successful treatment patients following artemisinin derivatives combination therapy.


Subject(s)
Adult , Antigens, Protozoan/genetics , Antimalarials/therapeutic use , Artemisinins/therapeutic use , Female , Gene Frequency , Genetic Variation , Genotype , Humans , Malaria, Falciparum/drug therapy , Male , Merozoite Surface Protein 1/genetics , Myanmar , Plasmodium falciparum/classification , Polymerase Chain Reaction , Protozoan Proteins/genetics , Thailand , Treatment Failure
15.
Mem. Inst. Oswaldo Cruz ; 108(8): 947-961, 6/dez. 2013. tab, graf
Article in English | LILACS | ID: lil-697142

ABSTRACT

The development and rapid spread of chloroquine resistance (CQR) in Plasmodium falciparum have triggered the identification of several genetic target(s) in the P. falciparum genome. In particular, mutations in the Pfcrt gene, specifically, K76T and mutations in three other amino acids in the region adjoining K76 (residues 72, 74, 75 and 76), are considered to be highly related to CQR. These various mutations form several different haplotypes and Pfcrt gene polymorphisms and the global distribution of the different CQR- Pfcrt haplotypes in endemic and non-endemic regions of P. falciparum malaria have been the subject of extensive study. Despite the fact that the Pfcrt gene is considered to be the primary CQR gene in P. falciparum , several studies have suggested that this may not be the case. Furthermore, there is a poor correlation between the evolutionary implications of the Pfcrt haplotypes and the inferred migration of CQR P. falciparum based on CQR epidemiological surveillance data. The present paper aims to clarify the existing knowledge on the genetic basis of the different CQR- Pfcrt haplotypes that are prevalent in worldwide populations based on the published literature and to analyse the data to generate hypotheses on the genetics and evolution of CQR malaria.


Subject(s)
Humans , Antimalarials/pharmacology , Chloroquine/pharmacology , Drug Resistance/genetics , Haplotypes/genetics , Malaria, Falciparum/parasitology , Membrane Transport Proteins/genetics , Plasmodium falciparum/genetics , Protozoan Proteins/genetics , DNA, Protozoan/genetics , Malaria, Falciparum/drug therapy , Polymorphism, Genetic , Plasmodium falciparum/drug effects
16.
Mem. Inst. Oswaldo Cruz ; 108(8): 968-973, 6/dez. 2013. tab, graf
Article in English | LILACS | ID: lil-697149

ABSTRACT

The emerging resistance to artemisinin derivatives that has been reported in South-East Asia led us to assess the efficacy of artemether-lumefantrine as the first line therapy for uncomplicated Plasmodium falciparum infections in Suriname. This drug assessment was performed according to the recommendations of the World Health Organization in 2011. The decreasing number of malaria cases in Suriname, which are currently limited to migrating populations and gold miners, precludes any conclusions on artemether efficacy because adequate numbers of patients with 28-day follow-up data are difficult to obtain. Therefore, a comparison of day 3 parasitaemia in a 2011 study and in a 2005/2006 study was used to detect the emergence of resistance to artemether. The prevalence of day 3 parasitaemia was assessed in a study in 2011 and was compared to that in a study in 2005/2006. The same protocol was used in both studies and artemether-lumefantrine was the study drug. Of 48 evaluable patients in 2011, 15 (31%) still had parasitaemia on day 3 compared to one (2%) out of 45 evaluable patients in 2005/2006. Overall, 11 evaluable patients in the 2011 study who were followed up until day 28 had negative slides and similar findings were obtained in all 38 evaluable patients in the 2005/2006 study. The significantly increased incidence of parasite persistence on day 3 may be an indication of emerging resistance to artemether.


Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Young Adult , Antimalarials/therapeutic use , Artemisinins/therapeutic use , Drug Resistance , Ethanolamines/therapeutic use , Fluorenes/therapeutic use , Malaria, Falciparum/parasitology , Parasitemia , Plasmodium falciparum/drug effects , Drug Combinations , Incidence , Malaria, Falciparum/drug therapy , Malaria, Falciparum/epidemiology , Parasitemia/epidemiology , Suriname/epidemiology
17.
Rev. Soc. Bras. Med. Trop ; 46(4): 525-527, Jul-Aug/2013. tab
Article in English | LILACS | ID: lil-683332

ABSTRACT

Artemisinin-based combination therapy-resistant malaria is rare in Sub-Saharan Africa. The World Health Organization identifies monitoring and surveillance using day-3 parasitaemia post-treatment as the standard test for identifying suspected artemisinin resistance. We report three cases of early treatment failure due to possible artemisinin-based combination therapy-resistant Plasmodium falciparum malaria. All cases showed adequate clinical and parasitological responses to quinine. This study reveals a need to re-evaluate the quality and efficacy of artemisinin-based combination therapy agents in Nigeria and Sub-Saharan Africa.


Subject(s)
Adult , Female , Humans , Middle Aged , Antimalarials/administration & dosage , Artemisinins/administration & dosage , Malaria, Falciparum/drug therapy , Quinine/administration & dosage , Antimalarials/adverse effects , Artemisinins/adverse effects , Drug Resistance , Drug Therapy, Combination/methods , Nigeria , Treatment Failure
18.
Saudi Medical Journal. 2013; 34 (6): 569-578
in English | IMEMR | ID: emr-130549

ABSTRACT

Current malaria treatments are based on the use of artemisinin based combinations. In the Kingdom of Saudi Arabia, the combination of pyrimethamine/sulfadoxine/artesunate is the first line of treatment of uncomplicated malaria, while lumefantrine/artemether [Coartem] is used as a second option. The treatment of severe malaria rests on the use of quinine or artesunate. In Saudi Arabia, most cases of malaria are imported, mainly from emigrant workers from the Indian subcontinent and the Eastern part of Africa. As a result, most parasites might have been exposed to antimalarials prior to coming to the country. Thus, knowledge of the pattern of resistance to these drugs outside the country could contribute to better management of the disease. In this review, we have summarized our current knowledge on the efficacy and resistance patterns of currently used antimalarials. Alternative treatments that could be used against malaria in the Kingdom are also discussed


Subject(s)
Antimalarials , Drug Resistance , Plasmodium falciparum/drug effects , Malaria, Falciparum/drug therapy , Antimalarials/pharmacology
20.
Rev. Soc. Bras. Med. Trop ; 45(6): 732-738, Nov.-Dec. 2012. mapas, tab
Article in English | LILACS | ID: lil-661076

ABSTRACT

INTRODUCTION: In Colombia, there are no published studies for the treatment of uncomplicated Plasmodium falciparum malaria comparing artemisinin combination therapies. Hence, it is intended to demonstrate the non-inferior efficacy/safety profiles of artesunate + amodiaquine versus artemether-lumefantrine treatments. METHODS: A randomized, controlled, open-label, noninferiority (Δ≤5%) clinical trial was performed in adults with uncomplicated P. falciparum malaria using the 28‑day World Health Organization validated design/definitions. Patients were randomized 1:1 to either oral artesunate + amodiaquine or artemether-lumefantrine. The primary efficacy endpoint: adequate clinical and parasitological response; secondary endpoints: - treatment failures defined per the World Health Organization. Safety: assessed through adverse events. RESULTS: A total of 105 patients was included in each group: zero censored observations. Mean (95%CI - Confidence interval) adequate clinical and parasitological response rates: 100% for artesunate + amodiaquine and 99% for artemether-lumefantrine; the noninferiority criteria was met (Δ=1.7%). There was one late parasitological therapeutic failure (1%; artemether-lumefantrine group), typified by polymerase chain reaction as the MAD20 MSP1 allele. The fever clearance time (artesunate + amodiaquine group) was significantly shorter (p=0.002). Respectively, abdominal pain for artesunate + amodiaquine and artemether-lumefantrine was 1.9% and 3.8% at baseline (p=0.68) and 1% and 13.3% after treatment (p<0.001). CONCLUSIONS: Uncomplicated P. falciparum malaria treatment with artesunate + amodiaquine is noninferior to the artemether-lumefantrine standard treatment. The efficacy/safety profiles grant further studies in this and similar populations.


INTRODUÇÃO: Na Colômbia não existem estudos publicados sobre o tratamento da malária não complicada por Plasmodium falciparum comparando as terapias combinadas com artemisinina. Destarte, quer se demonstrar a não inferioridade dos perfis de eficácia/segurança dos tratamentos com artesunato+amodiaquina versus artemeter-lumefantrina. MÉTODOS: Foi realizado um estudo clínico de não inferioridade (∆≤5%), aleatório, controlado, aberto, em adultos com malária não complicada por P. falciparum usando o desenho validado de 28 dias e os desenhos validados/definidos pela Organização Mundial da Saúde. Os pacientes foram aleatorizados (1:1) para ambos artesunato+amodiaquina ou artemeter-lumefantrina orais. Critérios primários de eficácia: resposta clínica e parasitológica adequada; Criterios de eficácia secundários: as falhas de tratamento definidos pela Organização Mundial da Saúde. A segurança: avaliada através de eventos adversos. RESULTADOS: Foram incursos 105 pacientes em cada grupo: zero observações censuradas. As taxas médias da resposta clínica e parasitológica adequada (95% IC - intervalo de confiança): 100% para artesunato+amodiaquina e 99% para artemeter-lumefantrina; atingiu-se o critério de não inferioridade (∆=1.7%). Houve uma falha terapêutica parasitológica tardia (1%; grupo artemeter-lumefantrina), caracterizada mediante reação em cadeia da polimerase como o alelo MAD20 MSP1. Tempo de remissão da febre (grupo artesunato+amodiaquina), foi significativamente mais curto (p=0.002). Dor abdominal, para artesunato+amodiaquina e artemeter-lumefantrina, respectivamente, 1.9% e 3.8% (p=0.68) na linha de base, 1% e 13.3% pós-tratamento (p<0.001). CONCLUSÕES: O tratamento com artesunato+amodiaquina da malária não complicada por P. falciparum é não inferior ao tratamento normal com artemeter-lumefantrina. Os perfis de eficácia/segurança justificam estudos adicionais nesta e outras populações semelhantes.


Subject(s)
Adult , Female , Humans , Male , Amodiaquine/administration & dosage , Antimalarials/administration & dosage , Artemisinins/administration & dosage , Ethanolamines/administration & dosage , Fluorenes/administration & dosage , Malaria, Falciparum/drug therapy , Amodiaquine/adverse effects , Antimalarials/adverse effects , Artemisinins/adverse effects , Colombia , Drug Combinations , Drug Therapy, Combination/methods , Ethanolamines/adverse effects , Fluorenes/adverse effects , Treatment Outcome
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