Background: A marked decrease in malaria-related deaths worldwide has been attributed to the administration of effective antimalarials against Plasmodium falciparum. However, the continuous spread of P. falciparum res...Background: A marked decrease in malaria-related deaths worldwide has been attributed to the administration of effective antimalarials against Plasmodium falciparum. However, the continuous spread of P. falciparum resistance to anti-malarial drugs is raising a serious problem in controlling Malaria to the vulnerable children’s immune system. In recent studies, Plasmodium falciparum Kelch 13 propeller gene (Pfk13) has been reported to develop resistance to artemisinin in South Asia. In this study, we checked Plasmodium falciparum chloroquine resistance transporter gene (Pfcrt) involved in chloroquine (CQ) resistance. Method: In this study, archived 280 samples were collected from Alupe primary school children in Busia, Western Kenya from May, 2016 to November, 2016. Genomic DNA was extracted using the MightyPrep reagent. The samples were investigated for P. falciparum positivity out of which 67 of them tested positive giving a prevalence rate of 24%. The sixty-seven were subjected to PCR amplification for the molecular marker resistance to Pfcrt. After PCR amplification, the amplicons were purified and sequenced using Sanger Sequencing. The sequence data were analyzed using BioEdit software to identify point mutations. Results: 14 samples sequences were analyzed on Bioedit software giving the following amino acid changes F76C, Y66H, L70A, Y58C, T59V, V65I, P67L, T81L, Y60S, Y66S, P67T and I71F). New mutations have been reported at position 76 leading to an amino acid change, one of Pfcrt gold standard biomarkers. However, amino acid changes Y66H, L70A, Y58C, T59V, V65I, P67L, T81L, Y60S, Y66S, P67T and I71F are newly reported giving an increase in Pfcrt prevalence of concern from zero to 5.0%. A phylogenetic evolutionary relationship was constructed as shown below. Generally, the results showed a continuous resistance of P.falciparum to Pfcrt which calls for robust continuous monitoring and surveillance. Conclusion: Due to the increase of the resistant Pfcrt gene prevalence, continuous development of new mutants展开更多
目的评价美国Inverness medical professional diagnostics公司生产的疟原虫检测试剂卡的临床应用效果。方法以镜检方法作为金标准比较BinaxNOW疟原虫检测试剂卡临床应用效果。结果 400份样本用镜检方法和BinaxNOW疟原虫检测试剂卡...目的评价美国Inverness medical professional diagnostics公司生产的疟原虫检测试剂卡的临床应用效果。方法以镜检方法作为金标准比较BinaxNOW疟原虫检测试剂卡临床应用效果。结果 400份样本用镜检方法和BinaxNOW疟原虫检测试剂卡诊断,镜检法检出阳性138份,其中恶性疟77份、间日疟61份;疟原虫检测试剂卡检出阳性139例,其中恶性疟71份,间日疟68份。试剂卡检测疟疾的敏感度为98.55%,特异度为98.85%,检测恶性疟的灵敏度为87.01%、特异度为98.76%,检测间日疟的敏感度为93.44%、特异度为96.76%。存在交叉反应。结论BinaxNOW疟原虫检测试剂卡诊断疟疾敏感性与特异性高,操作简单,结果显示直观、快速,适合边远疟区无镜检能力的个体、乡村医生开展疟疾筛查。展开更多
Alternative therapies are necessary for the treatment of malaria due to emerging drug resistance.However,many promising antimalarial compounds have poor water solubility and suffer from the lack of suitable delivery s...Alternative therapies are necessary for the treatment of malaria due to emerging drug resistance.However,many promising antimalarial compounds have poor water solubility and suffer from the lack of suitable delivery systems,which seriously limits their activity.To address this problem,we synthesized a series of azacarbazoles that were evaluated for antimalarial activity against D10(chloroquine-sensitive)and W2(chloroquine-resistant)strains of P.falciparum.The most active compound,9H-3-azacarbazole(3),was encapsulated in a novel o/w nanoemulsion consisting of ethyl esters of polyunsaturated fatty acids n-3 and n-6 obtained from flax oil as the oil phase,Smix(Tween 80 and Transcutol HP)and water.This formulation was further analyzed using transmission electron microscopy,dynamic light scattering and in vitro and in vivo studies.It was shown that droplets of the 3-loaded nanosystem were spherical,with satisfactory stability,without cytotoxicity towards fibroblasts and intestinal cell lines at concentrations corresponding to twice the IC50 for P.falciparum.Moreover,the nanoemulsion with this type of oil phase was internalized by Caco-2 cells.Additionally,pharmacokinetics demonstrated rapid absorption of compound 3(tmax=5.0 min)after intragastric administration of 3-encapsulated nanoemulsion at a dose of 0.02 mg/kg in mice,with penetration of compound 3 to deep compartments.The 3-encapsulated nanoemulsion was found to be 2.8 and 4.2 times more effective in inhibiting the D10 and W2 strains of the parasite,respectively,compared to non-encapsulated 3.Our findings support a role for novel o/w nanoemulsions as delivery vehicles for antimalarial drugs.展开更多
文摘Background: A marked decrease in malaria-related deaths worldwide has been attributed to the administration of effective antimalarials against Plasmodium falciparum. However, the continuous spread of P. falciparum resistance to anti-malarial drugs is raising a serious problem in controlling Malaria to the vulnerable children’s immune system. In recent studies, Plasmodium falciparum Kelch 13 propeller gene (Pfk13) has been reported to develop resistance to artemisinin in South Asia. In this study, we checked Plasmodium falciparum chloroquine resistance transporter gene (Pfcrt) involved in chloroquine (CQ) resistance. Method: In this study, archived 280 samples were collected from Alupe primary school children in Busia, Western Kenya from May, 2016 to November, 2016. Genomic DNA was extracted using the MightyPrep reagent. The samples were investigated for P. falciparum positivity out of which 67 of them tested positive giving a prevalence rate of 24%. The sixty-seven were subjected to PCR amplification for the molecular marker resistance to Pfcrt. After PCR amplification, the amplicons were purified and sequenced using Sanger Sequencing. The sequence data were analyzed using BioEdit software to identify point mutations. Results: 14 samples sequences were analyzed on Bioedit software giving the following amino acid changes F76C, Y66H, L70A, Y58C, T59V, V65I, P67L, T81L, Y60S, Y66S, P67T and I71F). New mutations have been reported at position 76 leading to an amino acid change, one of Pfcrt gold standard biomarkers. However, amino acid changes Y66H, L70A, Y58C, T59V, V65I, P67L, T81L, Y60S, Y66S, P67T and I71F are newly reported giving an increase in Pfcrt prevalence of concern from zero to 5.0%. A phylogenetic evolutionary relationship was constructed as shown below. Generally, the results showed a continuous resistance of P.falciparum to Pfcrt which calls for robust continuous monitoring and surveillance. Conclusion: Due to the increase of the resistant Pfcrt gene prevalence, continuous development of new mutants
文摘目的评价美国Inverness medical professional diagnostics公司生产的疟原虫检测试剂卡的临床应用效果。方法以镜检方法作为金标准比较BinaxNOW疟原虫检测试剂卡临床应用效果。结果 400份样本用镜检方法和BinaxNOW疟原虫检测试剂卡诊断,镜检法检出阳性138份,其中恶性疟77份、间日疟61份;疟原虫检测试剂卡检出阳性139例,其中恶性疟71份,间日疟68份。试剂卡检测疟疾的敏感度为98.55%,特异度为98.85%,检测恶性疟的灵敏度为87.01%、特异度为98.76%,检测间日疟的敏感度为93.44%、特异度为96.76%。存在交叉反应。结论BinaxNOW疟原虫检测试剂卡诊断疟疾敏感性与特异性高,操作简单,结果显示直观、快速,适合边远疟区无镜检能力的个体、乡村医生开展疟疾筛查。
基金the statutory activity of subsidy from the Polish Ministry of Science and Higher Education for the Faculty of Biotechnology and Faculty of Chemistry of the University of Wroclaw and by Ministero dell’Istruzione,dell’Universit`a e della Ricerca[PRIN 2015.4JRJPP_004].Publication costs were supported by Wroclaw Center of Biotechnology program“The Leading National Research Center(KNOW)for years 2014-2018”.
文摘Alternative therapies are necessary for the treatment of malaria due to emerging drug resistance.However,many promising antimalarial compounds have poor water solubility and suffer from the lack of suitable delivery systems,which seriously limits their activity.To address this problem,we synthesized a series of azacarbazoles that were evaluated for antimalarial activity against D10(chloroquine-sensitive)and W2(chloroquine-resistant)strains of P.falciparum.The most active compound,9H-3-azacarbazole(3),was encapsulated in a novel o/w nanoemulsion consisting of ethyl esters of polyunsaturated fatty acids n-3 and n-6 obtained from flax oil as the oil phase,Smix(Tween 80 and Transcutol HP)and water.This formulation was further analyzed using transmission electron microscopy,dynamic light scattering and in vitro and in vivo studies.It was shown that droplets of the 3-loaded nanosystem were spherical,with satisfactory stability,without cytotoxicity towards fibroblasts and intestinal cell lines at concentrations corresponding to twice the IC50 for P.falciparum.Moreover,the nanoemulsion with this type of oil phase was internalized by Caco-2 cells.Additionally,pharmacokinetics demonstrated rapid absorption of compound 3(tmax=5.0 min)after intragastric administration of 3-encapsulated nanoemulsion at a dose of 0.02 mg/kg in mice,with penetration of compound 3 to deep compartments.The 3-encapsulated nanoemulsion was found to be 2.8 and 4.2 times more effective in inhibiting the D10 and W2 strains of the parasite,respectively,compared to non-encapsulated 3.Our findings support a role for novel o/w nanoemulsions as delivery vehicles for antimalarial drugs.
