在高度流行地区生活的儿童中无症状携带恶性疟原虫的现象独立于 IgG 应答发生,但与平衡的炎症细胞因子比值相关。

Asymptomatic carriage of Plasmodium falciparum in children living in a hyperendemic area occurs independently of IgG responses but is associated with a balanced inflammatory cytokine ratio.

机构信息

Molecular Parasitology Laboratory, Centre Pasteur du Cameroun, BP 1274, Yaounde, Cameroon.

Department of Animal Biology and Physiology of the University of Yaoundé I, BP 812, Yaounde, Cameroon.

出版信息

Malar J. 2024 Sep 4;23(1):268. doi: 10.1186/s12936-024-05086-8.

Abstract

BACKGROUND

Asymptomatic carriage of infected red blood cells (iRBCs) can be prevalent in communities regardless of transmission patterns and can occur with infection of different Plasmodium species. Clinical immunity dampens the inflammatory responses leading to disease symptoms in malaria. The aim of this study was to define the immunological correlates of asymptomatic carriage of Plasmodium falciparum in a highly exposed population.

METHODS

142 asymptomatic Plasmodium-infected individuals greater than 2 years of age without fever (body temperature <37.5 ℃) were followed weekly for 10 weeks before being treated with artemisinin-based combination therapy (ACT). Plasma levels of 38 cytokines were measured at baseline by Luminex and the quantity and growth inhibitory activities of circulating parasite-reactive antibodies measured. The Plasmodium antigen tested included P. falciparum merozoite extract (ME) and schizont extract (SE), and the recombinant proteins erythrocyte binding antigen 175 (EBA-175) and merozoite surface protein 1 (MSP-1).

RESULTS

Median levels of IgG against P. falciparum EBA-175 and MSP-1 at baseline were significantly higher in those older than 20 years of age compared with the younger age group and appeared to correlate with better parasite control. Amongst all participants there were no discernible changes in IgG levels over time. Parasite density was higher in the younger age group and associated with IL-10, TNF and MCP-1 levels. A balanced IL-10:TNF ratio was associated with asymptomatic malaria regardless of age, and balanced ratios of IL-10/TNF and IL-10/IFN-γ were the only significant correlate of maintenance of asymptomatic malaria over the course of the study in individuals 20 years of age and younger.

CONCLUSION

The above findings indicate that asymptomatic carriage of P. falciparum in children living in a hyperendemic area occurs independently of IgG but is associated with a balanced inflammatory cytokine ratio.

摘要

背景

无论传播模式如何,受感染的红细胞(iRBC)无症状携带在社区中可能很普遍,并且可能发生于不同的疟原虫物种感染。临床免疫抑制了导致疟疾症状的炎症反应。本研究的目的是定义高度暴露人群中无症状携带恶性疟原虫的免疫学相关性。

方法

142 名年龄大于 2 岁且无症状的感染恶性疟原虫个体(体温<37.5℃),在接受基于青蒿素的联合治疗(ACT)前,每周随访 10 周。通过 Luminex 在基线时测量 38 种细胞因子的血浆水平,并测量循环寄生虫反应性抗体的数量和生长抑制活性。检测的疟原虫抗原包括恶性疟原虫裂殖子提取物(ME)和裂殖体提取物(SE),以及重组蛋白红细胞结合抗原 175(EBA-175)和裂殖体表面蛋白 1(MSP-1)。

结果

与年龄较小的年龄组相比,20 岁以上个体的基线 IgG 针对恶性疟原虫 EBA-175 和 MSP-1 的中位水平显着更高,并且似乎与更好的寄生虫控制相关。在所有参与者中,IgG 水平随时间没有明显变化。年轻年龄组的寄生虫密度较高,与 IL-10、TNF 和 MCP-1 水平相关。IL-10:TNF 比值平衡与无症状疟疾相关,无论年龄大小,IL-10/TNF 和 IL-10/IFN-γ 的平衡比值是 20 岁及以下个体无症状疟疾持续存在的唯一重要相关因素。

结论

上述发现表明,生活在高度流行地区的儿童中无症状携带恶性疟原虫的发生与 IgG 无关,但与炎症细胞因子的平衡比值相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3474/11375831/0bcac5dc9cad/12936_2024_5086_Fig1_HTML.jpg

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