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喀麦隆不同疟疾流行地区儿童对恶性疟原虫裂殖子表面蛋白-1 和顶端膜蛋白-1 免疫应答的差异。

Variation in the immune responses against Plasmodium falciparum merozoite surface protein-1 and apical membrane antigen-1 in children residing in the different epidemiological strata of malaria in Cameroon.

机构信息

Department of Microbiology and Parasitology, University of Buea, P.B. 63, Buea, Cameroon.

Department of Medical Laboratory Sciences, University of Buea, P.B. 63, Buea, Cameroon.

出版信息

Malar J. 2017 Nov 9;16(1):453. doi: 10.1186/s12936-017-2105-4.

Abstract

BACKGROUND

Studies to assess the immune responses against malaria in Cameroonian children are limited. The purpose of this study was to assess the immune responses against Plasmodium falciparum merozoite surface protein-1 (MSP-1) and apical membrane antigen-1 (AMA-1) in children residing in the different epidemiological strata of malaria in Cameroon.

METHODS

In a cross-sectional survey performed between April and July 2015, 602 children between 2 and 15 years (mean ± SD = 5.7 ± 3.7), comprising 319 (53%) males were enrolled from five epidemiological strata of malaria in Cameroon including: the sudano-sahelian (SS) strata, the high inland plateau (HIP) strata, the south Cameroonian equatorial forest (SCEF) strata, the high western plateau (HWP) strata, and the coastal (C) strata. The children were screened for clinical malaria (defined by malaria parasitaemia ≥ 5000 parasites/µl plus axillary temperature ≥ 37.5 °C). Their antibody responses were measured against P. falciparum MSP-1 and AMA-1 vaccine candidate antigens using standard ELISA technique.

RESULTS

A majority of the participants were IgG responders 72.1% (95% CI 68.3-75.6). The proportion of responders was higher in females (p = 0.002) and in children aged 10 years and above (p = 0.005). The proportion of responders was highest in Limbe (C strata) and lowest in Ngaoundere (HIP strata) (p < 0.0001). Similarly, the mean IgG antibody levels were higher in children aged 10 years and above (p < 0.0001) and in Limbe (p = 0.001). The IgG antibody levels against AMA-1 were higher in females (p = 0.028), meanwhile no gender disparity was observed with MSP-1. Furthermore the risk of clinical malaria (p < 0.0001) and the mean parasite density (p = 0.035) were higher in IgG non-responders.

CONCLUSION

A high proportion of IgG responders was observed in this study, suggesting a high degree exposure of the target population to malaria parasites. The immune responses varied considerably across the different strata: the highest levels observed in the C strata and the lowest in the HIP strata. Furthermore, malaria transmission in Cameroon could be categorized into two major groups based on the serological reaction of the children: the southern (comprising C and SCEF strata) and northern (comprising HWP, HIP and SS strata) groups. These findings may have significant implications in the design of future trials for evaluating malaria vaccine candidates in Cameroon.

摘要

背景

评估喀麦隆儿童对疟疾免疫反应的研究有限。本研究旨在评估居住在喀麦隆不同疟疾流行病学区域的儿童对恶性疟原虫裂殖表面蛋白-1(MSP-1)和顶端膜抗原-1(AMA-1)的免疫反应。

方法

在 2015 年 4 月至 7 月期间进行的一项横断面研究中,纳入了来自喀麦隆五个疟疾流行病学区域的 602 名 2 至 15 岁的儿童(均值±标准差=5.7±3.7),包括 319 名(53%)男性。这些区域包括:苏丹-萨赫勒(SS)区域、高内陆高原(HIP)区域、南喀麦隆赤道森林(SCEF)区域、高西部高原(HWP)区域和沿海(C)区域。对儿童进行临床疟疾(定义为疟疾寄生虫血症≥5000 个寄生虫/µl 加上腋温≥37.5°C)筛查。使用标准 ELISA 技术测量他们对恶性疟原虫 MSP-1 和 AMA-1 候选疫苗抗原的抗体反应。

结果

大多数参与者是 IgG 应答者(72.1%[95%CI 68.3-75.6])。女性(p=0.002)和 10 岁及以上儿童(p=0.005)的应答者比例更高。在 Limbe(C 区域)的应答者比例最高,在 Ngaoundere(HIP 区域)的应答者比例最低(p<0.0001)。同样,10 岁及以上儿童的 IgG 抗体水平较高(p<0.0001),Limbe 地区的 IgG 抗体水平也较高(p=0.001)。女性的 AMA-1 IgG 抗体水平较高(p=0.028),而 MSP-1 则没有性别差异。此外,IgG 非应答者的临床疟疾风险(p<0.0001)和平均寄生虫密度(p=0.035)更高。

结论

本研究观察到 IgG 应答者的比例较高,这表明目标人群对疟原虫的暴露程度较高。免疫反应在不同区域之间存在显著差异:在 C 区域观察到最高水平,在 HIP 区域观察到最低水平。此外,喀麦隆的疟疾传播可以分为两个主要组,基于儿童的血清学反应:南部(包括 C 和 SCEF 区域)和北部(包括 HWP、HIP 和 SS 区域)。这些发现可能对未来在喀麦隆评估疟疾疫苗候选物的试验设计具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba32/5679504/5d6f4fa95ea2/12936_2017_2105_Fig1_HTML.jpg

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