Therapeutic Efficacy of Triple Regimen of Artemether, Lumefantrine and Hippocratea africana in the Treatment of Plasmodium berghei Infected Mice

A. Uwah, A. Bassey, Innocent Asukwo Edagha, Blessing Obinaju Effiong
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Abstract

Combination therapy is fast replacing monotherapy in the treatment of infectious diseases and Plasmodium resistance to artemisinin–based combination therapies (ACTs) is an emerging challenge. Our study aimed to evaluate the therapeutic efficacy of combining Artemether-Lumefantrine with crude root bark extract of Hippocratea africana, on mice infected with Plasmodium berghei. Forty-five albino mice which weighed 30 - 38g were grouped into five with seven mice in each. The mice were inoculated intraperitoneally with Plasmodium berghei and kept for seven days for the parasitaemia to develop. A daily single dose of 200mg/Kg body weight of extract of H. africana was administered orally for ten days, while therapeutic dose of Artemether-lumefantrine was administered as daily single dose to the relevant groups on the last six days of treatment. A non-parasitized and parasitize untreated groups served as controls. The weights of the animals were recorded before and after treatment. The animals were sacrificed and blood obtained for determination of percentage parasitaemia and the erythrocytes count of the parasitized mice using standard methods. The results showed the mean body weight and percentage body weight changes of parasitized mice treated with combination of ACT plus H. africana not statistically different from those of non-parasitized untreated mice. Parasitized mice treated with ACT plus Extract had a significantly (p < 0.05) reduced percentage parasitaemia when compared with those treated with ACT only. Treatment with ACT plus Extract also showed a significant increase in parasite clearance (100%) when compared to mice treated with either ACT only (93.10%) or Extract only (82.15%). We concluded that combining artemether, lumefantrine and H. africana root bark extract exhibited a good therapeutic efficacy as demonstrated by body weight recovery, parasite clearance and reversion of clinical signs induced by Plasmodium berghei parasitaemia. The triple regimen was more efficacious than ACT alone, and therefore, may be a useful regimen in addressing the emerging problem of resistance of plasmodium species to standards ACTs.
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蒿甲醚、氨苯曲明和非洲希波克拉底三联疗法治疗伯氏疟原虫感染小鼠的疗效观察
在治疗传染病方面,联合疗法正在迅速取代单一疗法,而疟原虫对以青蒿素为基础的联合疗法的耐药性是一个新出现的挑战。本研究旨在评价蒿甲醚-氨芳碱联合非洲希波克拉底根皮粗提取物对伯氏疟原虫感染小鼠的治疗效果。45只体重30 - 38克的白化小鼠被分成5组,每组7只。小鼠腹腔注射伯氏疟原虫,留置7 d,待寄生虫病发生。在治疗的最后6天,相关组以非洲麻提取物200mg/Kg体重每日单剂量口服10天,同时以蒿甲醚-氨苯曲明治疗剂量每日单剂量口服。未被寄生组和未被寄生组作为对照。记录治疗前后动物体重。处死动物,取血,用标准方法测定寄生小鼠的寄生率和红细胞计数。结果表明,ACT +非洲猿猴联合处理的被寄生小鼠的平均体重和体重百分比变化与未被寄生的未处理小鼠无统计学差异。与单用ACT处理相比,ACT加提取物处理小鼠的寄生率显著降低(p < 0.05)。与仅使用ACT(93.10%)或仅使用提取物(82.15%)的小鼠相比,ACT加提取物治疗也显示出寄生虫清除率(100%)的显著增加。我们认为蒿甲醚、甲苯芳碱和非洲木犀草根皮提取物联合使用具有良好的治疗效果,可以恢复体重,清除寄生虫,逆转伯氏疟原虫感染的临床症状。三联用药方案比单独使用青蒿素联合治疗更有效,因此可能是解决新出现的疟原虫对标准青蒿素联合治疗耐药问题的有效方案。
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