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一种用于评估传播阻断干预措施的疟疾志愿者感染研究的新型恶性疟原虫3D7库的传播性。

Transmissibility of a new Plasmodium falciparum 3D7 bank for use in malaria volunteer infection studies evaluating transmission blocking interventions.

作者信息

Lynch Sean A, Abd-Rahman Azrin N, Peters Jenny M, Heunis Juanita M, S E Gower Jeremy, Potter Adam J, Webster Rebecca, Jennings Helen, Mathison Susan, Sahai Nischal, Amante Fiona H, Barber Bridget E

机构信息

QIMR Berghofer, 300 Herston Rd, Herston, Brisbane, QLD, 4006, Australia.

Faculty of Health, School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, QLD, Australia.

出版信息

Sci Rep. 2025 Apr 16;15(1):13094. doi: 10.1038/s41598-025-97282-y.

Abstract

Transmission blocking activity is an important characteristic of antimalarial drugs, and can be evaluated in malaria volunteer infection studies (VIS). We undertook a pilot VIS to evaluate the suitability of a recently manufactured Plasmodium falciparum 3D7 bank (3D7-MBE-008) for evaluating transmission blocking interventions. Four adults were inoculated with P. falciparum 3D7-MBE-008 infected erythrocytes and administered piperaquine on days 8 and 10 to clear asexual parasitemia while permitting gametocyte development. On day 25, participants were randomised (1:1) to receive either 0.25 mg/kg primaquine (primaquine group) or no intervention (control group). Transmissibility was assessed by enriched membrane feeding assays on days 25, 29, 32, and 39, with transmission intensity (proportion of mosquitoes infected) determined by 18S qPCR. All participants were infective on day 25, with a median 94% (range, 12-100%) of mosquitoes positive for oocysts, and 76% (range, 8-94%) positive for sporozoites. In the primaquine group, mosquito infectivity decreased substantially between days 25 and 29. In the control group, mosquito infectivity remained high up to day 32, and persisted to day 39 in one participant. The P. falciparum 3D7-MBE-008 parasite bank induced blood-stage infections that were highly transmissible to mosquitoes and is therefore suitable for evaluating transmission blocking interventions.Trial registration anzctr.org.au (registration number: ACTRN12622001097730), registered 08/08/2022.

摘要

传播阻断活性是抗疟药物的一个重要特性,可在疟疾志愿者感染研究(VIS)中进行评估。我们开展了一项VIS试点研究,以评估最近生产的恶性疟原虫3D7库(3D7-MBE-008)用于评估传播阻断干预措施的适用性。四名成年人接种了感染恶性疟原虫3D7-MBE-008的红细胞,并在第8天和第10天给予哌喹以清除无性疟原虫血症,同时允许配子体发育。在第25天,参与者被随机分组(1:1),分别接受0.25mg/kg的伯氨喹(伯氨喹组)或不进行干预(对照组)。在第25、29、32和39天通过富集膜饲法评估传播性,通过18S qPCR确定传播强度(感染蚊子的比例)。所有参与者在第25天均具有传染性,感染卵囊的蚊子中位数为94%(范围为12-100%),感染子孢子的蚊子为76%(范围为8-94%)。在伯氨喹组中,蚊子的传染性在第25天至29天之间大幅下降。在对照组中,蚊子的传染性在第32天之前一直很高,一名参与者的传染性持续到第39天。恶性疟原虫3D7-MBE-008寄生虫库引发的血液阶段感染对蚊子具有高度传染性,因此适用于评估传播阻断干预措施。试验注册anzctr.org.au(注册号:ACTRN12622001097730),于2022年8月8日注册。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3af7/12003780/1921c1d27b76/41598_2025_97282_Fig1_HTML.jpg

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