Safety and PCR monitoring in 161 semi-immune Kenyan adults following controlled human malaria infection.
Safety and PCR monitoring in 161 semi-immune Kenyan adults following controlled human malaria infection.
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DOI：
10.1172/jci.insight.146443
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发表时间：
2021-09-08
期刊：
影响因子：
8
通讯作者：
Controlled Human Malaria Infection in Semi-Immune Kenyan Adults (CHMI-SIKA) Study Team
中科院分区：
文献类型：
--
作者：
Kapulu MC;Njuguna P;Hamaluba M;Kimani D;Ngoi JM;Musembi J;Ngoto O;Otieno E;Billingsley PF;Controlled Human Malaria Infection in Semi-Immune Kenyan Adults (CHMI-SIKA) Study Team
对疟疾的自然获得性免疫尚不完全了解。我们使用控制的人类疟疾感染（CHMI）来研究过去暴露对肯尼亚成年人疟疾与非肯尼亚寄生虫菌株感染的影响。通过直接静脉接种纯化、低温保存的恶性疟原虫孢子体（Sanaria PfSPZ Challenge， NF54西非菌株）3.2 × 103个，进行临床监测和18S核糖体RNA基因的连续定量PCR （qPCR）。当寄生虫量达到每μL血500或更多，出现临床重要症状，或接种后21天达到研究终点。所有志愿者在达到终点后都接受了抗疟药物治疗。161名志愿者在2016年8月4日至2018年2月14日期间接受了CHMI。CHMI耐受性良好，无严重或严重不良事件。19名志愿者（11.8%）因检测到抗疟药物高于最低抑制浓度或寄生虫基因分型为非nf54而被排除在分析之外。在符合分析条件的142名志愿者中，26名（18.3%）有发热症状并接受了治疗；30株（21.1%）每μL寄生虫500以上；53例（37.3%）寄生虫病未达到治疗阈值；33例（23.2%）qPCR阴性。我们发现，一些肯尼亚成年人过去暴露于疟疾，正如居住地所证明的那样，可以完全抑制来自肯尼亚境外的寄生虫菌株在体内的生长。ClinicalTrials.gov NCT02739763。威康信托基金会。
Naturally acquired immunity to malaria is incompletely understood. We used controlled human malaria infection (CHMI) to study the impact of past exposure on malaria in Kenyan adults in relation to infection with a non-Kenyan parasite strain. We administered 3.2 × 103 aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (Sanaria PfSPZ Challenge, NF54 West African strain) by direct venous inoculation and undertook clinical monitoring and serial quantitative PCR (qPCR) of the 18S ribosomal RNA gene. The study endpoint was met when parasitemia reached 500 or more parasites per μL blood, clinically important symptoms were seen, or at 21 days after inoculation. All volunteers received antimalarial drug treatment upon meeting the endpoint. One hundred and sixty-one volunteers underwent CHMI between August 4, 2016, and February 14, 2018. CHMI was well tolerated, with no severe or serious adverse events. Nineteen volunteers (11.8%) were excluded from the analysis based on detection of antimalarial drugs above the minimal inhibitory concentration or parasites genotyped as non-NF54. Of the 142 volunteers who were eligible for analysis, 26 (18.3%) had febrile symptoms and were treated; 30 (21.1%) reached 500 or more parasites per μL and were treated; 53 (37.3%) had parasitemia without meeting thresholds for treatment; and 33 (23.2%) remained qPCR negative. We found that past exposure to malaria, as evidenced by location of residence, in some Kenyan adults can completely suppress in vivo growth of a parasite strain originating from outside Kenya. ClinicalTrials.gov NCT02739763. Wellcome Trust.
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