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14 年的分子监测证实,在印度尼西亚巴布亚实施基于青蒿素的联合疗法后,间日疟原虫和恶性疟原虫的传播得到了减少。

Molecular surveillance over 14 years confirms reduction of Plasmodium vivax and falciparum transmission after implementation of Artemisinin-based combination therapy in Papua, Indonesia.

机构信息

Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia.

Eijkman Institute for Molecular Biology, Jakarta, Indonesia.

出版信息

PLoS Negl Trop Dis. 2020 May 7;14(5):e0008295. doi: 10.1371/journal.pntd.0008295. eCollection 2020 May.

DOI:10.1371/journal.pntd.0008295
PMID:32379762
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7237043/
Abstract

Genetic epidemiology can provide important insights into parasite transmission that can inform public health interventions. The current study compared long-term changes in the genetic diversity and structure of co-endemic Plasmodium falciparum and P. vivax populations. The study was conducted in Papua Indonesia, where high-grade chloroquine resistance in P. falciparum and P. vivax led to a universal policy of Artemisinin-based Combination Therapy (ACT) in 2006. Microsatellite typing and population genetic analyses were undertaken on available isolates collected between 2004 and 2017 from patients with uncomplicated malaria (n = 666 P. falciparum and n = 615 P. vivax). The proportion of polyclonal P. falciparum infections fell from 28% (38/135) before policy change (2004-2006) to 18% (22/125) at the end of the study (2015-2017); p<0.001. Over the same period, polyclonal P. vivax infections fell from 67% (80/119) to 35% (33/93); p<0.001. P. falciparum strains persisted for up to 9 years compared to 3 months for P. vivax, reflecting higher rates of outbreeding in the latter. Sub-structure was observed in the P. falciparum population, but not in P. vivax, confirming different patterns of outbreeding. The P. falciparum population exhibited 4 subpopulations that changed in frequency over time. Notably, a sharp rise was observed in the frequency of a minor subpopulation (K2) in the late post-ACT period, accounting for 100% of infections in late 2016-2017. The results confirm epidemiological evidence of reduced P. falciparum and P. vivax transmission over time. The smaller change in P. vivax population structure is consistent with greater outbreeding associated with relapsing infections and highlights the need for radical cure to reduce recurrent infections. The study emphasizes the challenge in disrupting P. vivax transmission and demonstrates the potential of molecular data to inform on the impact of public health interventions.

摘要

遗传流行病学可以为寄生虫传播提供重要的见解,从而为公共卫生干预措施提供信息。本研究比较了共患恶性疟原虫和间日疟原虫种群遗传多样性和结构的长期变化。该研究在印度尼西亚巴布亚进行,那里恶性疟原虫和间日疟原虫的高度耐氯喹导致 2006 年普遍采用青蒿素为基础的联合疗法(ACT)。对 2004 年至 2017 年间从患有无并发症疟疾的患者中采集的可用分离株(恶性疟原虫 n = 666,间日疟原虫 n = 615)进行了微卫星分型和种群遗传分析。政策变化前(2004-2006 年)多克隆恶性疟原虫感染的比例为 28%(38/135),研究结束时(2015-2017 年)降至 18%(22/125);p<0.001。同期,多克隆间日疟原虫感染从 67%(80/119)下降至 35%(33/93);p<0.001。恶性疟原虫株的持续时间长达 9 年,而间日疟原虫株的持续时间仅为 3 个月,反映了后者更高的杂交率。在恶性疟原虫种群中观察到亚结构,但在间日疟原虫中没有观察到,证实了不同的杂交模式。恶性疟原虫种群显示出 4 个亚种群,随着时间的推移其频率发生了变化。值得注意的是,在 ACT 后期,一个较小的亚种群(K2)的频率急剧上升,占 2016 年底至 2017 年期间所有感染的 100%。结果证实了随着时间的推移恶性疟原虫和间日疟原虫传播减少的流行病学证据。间日疟原虫种群结构变化较小,与复发感染相关的杂交率较高相一致,这突出表明需要根治性治疗来减少复发性感染。该研究强调了打破间日疟原虫传播的挑战,并展示了分子数据为公共卫生干预措施的影响提供信息的潜力。

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