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肯尼亚成年人经控制的人体疟疾感染(CHMI)的结果与既往疟疾暴露史和裂殖体抗体反应相关。

Controlled human malaria infection (CHMI) outcomes in Kenyan adults is associated with prior history of malaria exposure and anti-schizont antibody response.

机构信息

Centre for Geographic Medicine Research (Coast), Kenya Medical Research Institute-Wellcome Trust Research Programme, P. O. Box 230, Kilifi, 80108, Kenya.

Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University Oxford, Oxford, OX3 7LG, UK.

出版信息

BMC Infect Dis. 2022 Jan 24;22(1):86. doi: 10.1186/s12879-022-07044-8.

Abstract

BACKGROUND

Individuals living in endemic areas acquire immunity to malaria following repeated parasite exposure. We sought to assess the controlled human malaria infection (CHMI) model as a means of studying naturally acquired immunity in Kenyan adults with varying malaria exposure.

METHODS

We analysed data from 142 Kenyan adults from three locations representing distinct areas of malaria endemicity (Ahero, Kilifi North and Kilifi South) enrolled in a CHMI study with Plasmodium falciparum sporozoites NF54 strain (Sanaria® PfSPZ Challenge). To identify the in vivo outcomes that most closely reflected naturally acquired immunity, parameters based on qPCR measurements were compared with anti-schizont antibody levels and residence as proxy markers of naturally acquired immunity.

RESULTS

Time to endpoint correlated more closely with anti-schizont antibodies and location of residence than other parasite parameters such as growth rate or mean parasite density. Compared to observational field-based studies in children where 0.8% of the variability in malaria outcome was observed to be explained by anti-schizont antibodies, in the CHMI model the dichotomized anti-schizont antibodies explained 17% of the variability.

CONCLUSIONS

The CHMI model is highly effective in studying markers of naturally acquired immunity to malaria. Trial registration Clinicaltrials.gov number NCT02739763. Registered 15 April 2016.

摘要

背景

生活在疟疾流行地区的个体在反复受到寄生虫感染后会获得对疟疾的免疫力。我们试图评估人体疟疾感染控制(CHMI)模型,作为研究肯尼亚成年人自然获得性免疫力的一种手段,这些成年人的疟疾暴露情况各不相同。

方法

我们分析了来自三个不同疟疾流行地区(Ahero、Kilifi North 和 Kilifi South)的 142 名肯尼亚成年人的数据,这些成年人参加了 Plasmodium falciparum sporozoites NF54 株(Sanaria® PfSPZ Challenge)的 CHMI 研究。为了确定最能反映自然获得性免疫力的体内结果,我们将基于 qPCR 测量的参数与抗裂殖体抗体水平和居住地(作为自然获得性免疫力的替代标志物)进行了比较。

结果

与其他寄生虫参数(如增长率或平均寄生虫密度)相比,终点时间与抗裂殖体抗体和居住地的相关性更密切。与儿童中观察性基于现场的研究相比,在该研究中,疟疾结局的 0.8%的可变性被抗裂殖体抗体解释,而在 CHMI 模型中,二分类抗裂殖体抗体解释了 17%的可变性。

结论

CHMI 模型在研究疟疾自然获得性免疫力的标志物方面非常有效。试验注册Clinicaltrials.gov 编号 NCT02739763。于 2016 年 4 月 15 日注册。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9472/8785454/3a9f8bea7984/12879_2022_7044_Fig1_HTML.jpg

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