Comparison of Antibody Responses and Parasite Clearance in Artemisinin Therapeutic Efficacy Studies in the Democratic Republic of Congo and Asia

J. Cutts, Katherine O’Flaherty, S. Zaloumis, E. Ashley, Jo-Anne Chan, M. Onyamboko, Caterina A Fanello, A. Dondorp, Nicholas P J Day, A. Phyo, M. Dhorda, M. Imwong, R. Fairhurst, Pharath Lim, C. Amaratunga, S. Pukrittayakamee, T. Hien, Y. Htut, M. Mayxay, M. Faiz, E. Takashima, T. Tsuboi, J. Beeson, F. Nosten, J. Simpson, N. White, F. Fowkes
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引用次数: 1

Abstract

Abstract Background Understanding the effect of immunity on Plasmodium falciparum clearance is essential for interpreting therapeutic efficacy studies designed to monitor emergence of artemisinin drug resistance. In low-transmission areas of Southeast Asia, where resistance has emerged, P. falciparum antibodies confound parasite clearance measures. However, variation in naturally acquired antibodies across Asian and sub-Saharan African epidemiological contexts and their impact on parasite clearance re yet to be quantified. Methods In an artemisinin therapeutic efficacy study, antibodies to 12 pre-erythrocytic and erythrocytic P. falciparum antigens were measured in 118 children with uncomplicated P. falciparum malaria in the Democratic Republic of Congo (DRC) and compared with responses in patients from Asian sites, described elsewhere. Results Parasite clearance half-life was shorter in DRC patients (median, 2 hours) compared with most Asian sites (median, 2–7 hours), but P. falciparum antibody levels and seroprevalences were similar. There was no evidence for an association between antibody seropositivity and parasite clearance half-life (mean difference between seronegative and seropositive, −0.14 to +0.40 hour) in DRC patients. Conclusions In DRC, where artemisinin remains highly effective, the substantially shorter parasite clearance time compared with Asia was not explained by differences in the P. falciparum antibody responses studied.
刚果民主共和国和亚洲青蒿素治疗疗效研究中抗体反应和寄生虫清除的比较
背景了解免疫对恶性疟原虫清除的影响对于解释旨在监测青蒿素耐药出现的治疗疗效研究至关重要。在已出现耐药性的东南亚低传播地区,恶性疟原虫抗体混淆了寄生虫清除措施。然而,在亚洲和撒哈拉以南非洲流行病学背景下,自然获得性抗体的差异及其对寄生虫清除的影响仍有待量化。方法在一项青蒿素治疗效果研究中,对118名刚果民主共和国(DRC)无并发症恶性疟原虫疟疾患儿的12种红细胞前和红细胞恶性疟原虫抗原进行抗体检测,并与其他地方描述的亚洲地区患者的反应进行比较。结果刚果民主共和国患者的寄生虫清除半衰期(中位数为2小时)比大多数亚洲地区(中位数为2 - 7小时)短,但恶性疟原虫抗体水平和血清患病率相似。在刚果民主共和国患者中,没有证据表明抗体血清阳性与寄生虫清除半衰期(血清阴性和血清阳性之间的平均差异,−0.14至+0.40小时)之间存在关联。在刚果民主共和国,青蒿素仍然非常有效,但与亚洲相比,疟原虫清除时间明显较短,这并不能用所研究的恶性疟原虫抗体反应的差异来解释。
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