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婴幼儿时期感染疟原虫对马拉维儿童自然获得性疟疾免疫力发展的影响。

The impact of early life exposure to Plasmodium falciparum on the development of naturally acquired immunity to malaria in young Malawian children.

机构信息

The Department of Medicine (RMH), Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, 3000, Australia.

Department of Zoology, University of Dhaka, Dhaka, 1000, Bangladesh.

出版信息

Malar J. 2019 Jan 18;18(1):11. doi: 10.1186/s12936-019-2647-8.

DOI:10.1186/s12936-019-2647-8
PMID:30658632
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6339377/
Abstract

BACKGROUND

Antibodies targeting malaria blood-stage antigens are important targets of naturally acquired immunity, and may act as valuable biomarkers of malaria exposure.

METHODS

Six-hundred and one young Malawian children from a randomized trial of prenatal nutrient supplementation with iron and folic acid or pre- and postnatal multiple micronutrients or lipid-based nutrient supplements were followed up weekly at home and febrile episodes were investigated for malaria from birth to 18 months of age. Antibodies were measured for 601 children against merozoite surface proteins (MSP1 19kD, MSP2), erythrocyte binding antigen 175 (EBA175), reticulocyte binding protein homologue 2 (Rh2A9), schizont extract and variant surface antigens expressed by Plasmodium falciparum-infected erythrocytes (IE) at 18 months of age. The antibody measurement data was related to concurrent malaria infection and to documented episodes of clinical malaria.

RESULTS

At 18 months of age, antibodies were significantly higher among parasitaemic than aparasitaemic children. Antibody levels against MSP1 19kD, MSP2, schizont extract, and IE variant surface antigens were significantly higher in children who had documented episodes of malaria than in children who did not. Antibody levels did not differ between children with single or multiple malaria episodes before 18 months, nor between children who had malaria before 6 months of age or between 6 and 18 months.

CONCLUSIONS

Antibodies to merozoite and IE surface antigens increased following infection in early childhood, but neither age at first infection nor number of malaria episodes substantially affected antibody acquisition. These findings have implications for malaria surveillance during early childhood in the context of elimination. Trials registration Clinical Trials Registration: NCT01239693 (Date of registration: 11-10-2010). URL: http://www.ilins.org.

摘要

背景

针对疟原虫血期抗原的抗体是天然免疫的重要靶标,可能是疟疾暴露的有价值的生物标志物。

方法

601 名来自马拉维的年轻儿童参与了一项随机试验,该试验对产前铁和叶酸补充剂或产前和产后多种微量营养素或基于脂质的营养补充剂进行了补充,从出生到 18 个月大时每周在家中进行随访,并对发热病例进行疟疾调查。在 18 个月时,对 601 名儿童针对裂殖子表面蛋白(MSP1 19kD、MSP2)、红细胞结合抗原 175(EBA175)、网织红细胞结合蛋白同源物 2(Rh2A9)、裂殖体提取物和恶性疟原虫感染红细胞表达的变异表面抗原(IE)进行了抗体测量。抗体测量数据与同期疟疾感染和记录的临床疟疾发作有关。

结果

在 18 个月时,寄生虫血症儿童的抗体水平明显高于无寄生虫血症儿童。与无疟疾发作的儿童相比,有记录的疟疾发作儿童的 MSP1 19kD、MSP2、裂殖体提取物和 IE 变异表面抗原抗体水平明显更高。在 18 个月之前,有单次或多次疟疾发作的儿童之间的抗体水平没有差异,也没有在 6 个月之前或 6 至 18 个月之间感染疟疾的儿童之间存在差异。

结论

在儿童早期感染后,针对裂殖子和 IE 表面抗原的抗体增加,但首次感染年龄或疟疾发作次数均未对抗体获得产生重大影响。这些发现对消除疟疾背景下儿童早期疟疾监测具有重要意义。

试验注册

临床试验注册:NCT01239693(注册日期:2010 年 10 月 11 日)。网址:http://www.ilins.org。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b4a/6339377/c830b1b35978/12936_2019_2647_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b4a/6339377/ecb13271b302/12936_2019_2647_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b4a/6339377/c830b1b35978/12936_2019_2647_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b4a/6339377/ecb13271b302/12936_2019_2647_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b4a/6339377/c830b1b35978/12936_2019_2647_Fig2_HTML.jpg

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