Validation of the Micronutrient and Environmental Enteric Dysfunction Assessment Tool and evaluation of biomarker risk factors for growth faltering and vaccine failure in young Malian children.
Validation of the Micronutrient and Environmental Enteric Dysfunction Assessment Tool and evaluation of biomarker risk factors for growth faltering and vaccine failure in young Malian children.
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DOI：
10.1371/journal.pntd.0008711
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发表时间：
2020-09
影响因子：
3.8
通讯作者：
Choy RKM
中科院分区：
文献类型：
--
作者：
Arndt MB;Cantera JL;Mercer LD;Kalnoky M;White HN;Bizilj G;Boyle DS;de Hostos EL;Choy RKM
环境肠功能障碍 (EED) 是资源匮乏地区儿童中常见的一种肠道疾病，与生长迟缓、认知缺陷和口服疫苗免疫原性降低的风险增加有关。微量营养素和 EED 评估工具 (MEEDAT) 是一种多重免疫分析，可测量先前与儿童生长迟缓和/或口服疫苗免疫原性相关的生物标志物：肠脂肪酸结合蛋白 (I-FABP)、可溶性 CD14 (sCD14)、胰岛素样生长因子 1 (IGF-1) 和成纤维细胞生长因子 21 (FGF21)。 MEEDAT 还可以测量全身炎症（α1-酸性糖蛋白、C 反应蛋白）、铁蛋白、可溶性转铁蛋白受体、视黄醇结合蛋白 4、甲状腺球蛋白和恶性疟原虫抗原血症（富含组氨酸的蛋白 2）。使用来自马里婴儿临床试验参与者的 300 个样本，将 MEEDAT 的性能与市售酶联免疫吸附测定 (ELISA) 进行比较。使用回归方法来测试 MEEDAT 生物标志物是否与 28 天后血清转化为 A 型脑膜炎球菌结合疫苗 (MenAV)、黄热病疫苗 (YFV) 和五价轮状病毒疫苗 (PRV) 相关，或与 12 周内生长缓慢相关。对于血清 I-FABP、sCD14、IGF-1 和 FGF21，MEEDAT 和 ELISA 结果之间的 Pearson 相关性分别为 0.97、0.86、0.80 和 0.97。 I-FABP 浓度与 PRV IgG 血清转化概率之间以及 IGF-1 浓度与 YFV 血清转化概率之间存在显着相关性。在多变量模型中，两种相关性均不显着，但 AGP 浓度与 YFV 血清转化之间存在显着负相关。在多变量模型中，GLP-2 和 sCD14 浓度与年龄别体重 z 分数和身高别体重 z 分数的 12 周变化显着负相关。与市售 ELISA 相比，MEEDAT 在测量 EED 和生长激素耐药性的四种分析物方面表现良好。在资源匮乏地区采用 MEEDAT 有助于加速确定预防或治疗儿童发育迟缓的干预措施以及提高儿童疫苗接种免疫原性的干预措施。环境性肠功能障碍 (EED) 是资源匮乏地区儿童中常见的一种肠道疾病，与生长迟缓、认知缺陷和口服疫苗免疫原性降低的风险增加有关。识别患有 EED 的病态后遗症风险最高的儿童的一个关键挑战是缺乏经过验证的预测生物标志物。正在进行的临床研究正在有发育迟缓风险的儿童群体中测试和验证 EED 生物标志物，但测试多种生物标志物通常需要专门的设备、复杂的方法、资源和大量的努力。微量营养素和 EED 评估工具 (MEEDAT) 是一种多重免疫测定法，可测量与儿童生长迟缓和口服疫苗免疫原性相关的生物标志物，以及指示全身炎症和微量营养素缺乏的生物标志物。在本研究中，MEEDAT 的性能与对生活在资源匮乏环境中的儿童样本进行的商业单重检测具有良好的相关性。 MEEDAT 生物标志物与多种疫苗的生长结果和血清转化相关。 MEEDAT 有可能减少评估针对 EED 的干预措施的影响的时间和成本。
Environmental enteric dysfunction (EED) is an intestinal disorder common among children in low-resource settings and is associated with increased risk of growth stunting, cognitive deficits, and reduced oral vaccine immunogenicity. The Micronutrient and EED Assessment Tool (MEEDAT) is a multiplexed immunoassay that measures biomarkers previously associated with child growth faltering and/or oral vaccine immunogenicity: intestinal fatty acid–binding protein (I-FABP), soluble CD14 (sCD14), insulin-like growth factor 1 (IGF-1), and fibroblast growth factor 21 (FGF21). MEEDAT also measures systemic inflammation (α1-acid glycoprotein, C-reactive protein), ferritin, soluble transferrin receptor, retinol binding protein 4, thyroglobulin, and Plasmodium falciparum antigenemia (histidine-rich protein 2). The performance of MEEDAT was compared with commercially available enzyme-linked immunosorbent assays (ELISAs) using 300 specimens from Malian infant clinical trial participants. Regression methods were used to test if MEEDAT biomarkers were associated with seroconversion to meningococcal A conjugate vaccine (MenAV), yellow fever vaccine (YFV), and pentavalent rotavirus vaccine (PRV) after 28 days, or with growth faltering over 12 weeks. The Pearson correlations between the MEEDAT and ELISA results were 0.97, 0.86, 0.80, and 0.97 for serum I-FABP, sCD14, IGF-1, and FGF21, respectively. There were significant associations between I-FABP concentration and the probability of PRV IgG seroconversion and between IGF-1 concentration and the probability of YFV seroconversion. In multivariable models neither association remained significant, however there was a significant negative association between AGP concentration and YFV seroconversion. GLP-2 and sCD14 concentrations were significantly negatively associated with 12-week change in weight-for-age z-score and weight-for-height z-score in multivariable models. MEEDAT performed well in comparison to commercially-available ELISAs for the measurement of four analytes for EED and growth hormone resistance. Adoption of MEEDAT in low-resource settings could help accelerate the identification of interventions that prevent or treat child stunting and interventions that boost the immunogenicity of child vaccinations. Environmental enteric dysfunction (EED) is an intestinal disorder common among children in low-resource settings and has been associated with increased risk of growth stunting, cognitive deficits, and reduced oral vaccine immunogenicity. A key challenge to identifying children with EED at highest risk of morbid sequelae is the lack of validated predictive biomarkers. Ongoing clinical studies are testing and validating EED biomarkers in child populations at risk for stunting, yet testing multiple biomarkers commonly requires specialized equipment, complex methods, resources, and considerable effort. The Micronutrient and EED Assessment Tool (MEEDAT) is a multiplexed immunoassay that measures biomarkers associated with child growth faltering and oral vaccine immunogenicity, and biomarkers indicative of systemic inflammation and micronutrient deficiencies. The performance of MEEDAT was well-correlated with commercial monoplex assays in specimens from children living in a low-resource setting in the present study. MEEDAT biomarkers were associated with growth outcomes and seroconversion in response to several vaccines. MEEDAT has the potential to reduce the time and cost of evaluating impact of interventions targeting EED.
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影响因子：
3.7
作者：
Guerrant RL;Leite AM;Pinkerton R;Medeiros PH;Cavalcante PA;DeBoer M;Kosek M;Duggan C;Gewirtz A;Kagan JC;Gauthier AE;Swann J;Mayneris-Perxachs J;Bolick DT;Maier EA;Guedes MM;Moore SR;Petri WA;Havt A;Lima IF;Prata MM;Michaleckyj JC;Scharf RJ;Sturgeon C;Fasano A;Lima AA
通讯作者：
Lima AA
影响因子：
11.1
作者：
Naylor C;Lu M;Haque R;Mondal D;Buonomo E;Nayak U;Mychaleckyj JC;Kirkpatrick B;Colgate R;Carmolli M;Dickson D;van der Klis F;Weldon W;Steven Oberste M;PROVIDE study teams;Ma JZ;Petri WA Jr
通讯作者：
Petri WA Jr
影响因子：
11.1
作者：
Amadi B;Besa E;Zyambo K;Kaonga P;Louis-Auguste J;Chandwe K;Tarr PI;Denno DM;Nataro JP;Faubion W;Sailer A;Yeruva S;Brantner T;Murray J;Prendergast AJ;Turner JR;Kelly P
通讯作者：
Kelly P
影响因子：
11.8
作者：
Keusch, Gerald T.;Denno, Donna M.;Brewer, Thomas
通讯作者：
Brewer, Thomas
影响因子：
13.6
作者：
Korpe PS;Petri WA Jr
通讯作者：
Petri WA Jr