目的比较HemoCue@hb301仪(以下简称HemoCue仪)和Sysmex全自动血液分析仪测定血红蛋白水平的相关性和一致性,评估HemoCue仪检测血红蛋白(hemoglobin,Hb)应用于现场人群调查的适用性。方法用HemoCue仪和Sysmex全自动血液分析仪对相同的100例人体全血标本进行检测,比较两者测定的Hb值的相关性和一致性。采用随机数字法选取45份标本并分成3组,每份标本再平均分成4份,分别在常温,-4℃与-20℃条件下储存不同时间(12,24,36和48h)后用HemoCue仪测定Hb含量,比较不同储存温度和时间对检测结果的影响。结果两种方法的检测结果具有较好的相关性,r=0.995,但HemoCue仪测定值较Sysmex高,两者差异有统计学意义(t=11.471,P <0.001)。两种方法的一致性较好,LoA为(1.8,14.4)。HemoCue仪诊断贫血的灵敏度为58.62%,特异度为100%,阳性预测值为100%,阴性预测值为85.54%。三次重复测量的组间相关系数ICC为0.996,95%CI 0.993～0.997。常温下与-20℃下分别储存0～48 h后,Hb值略有升高趋势。4℃组储存条件下Hb含量相对稳定。结论 HemoCue仪在检测Hb含量有较好的一致性和稳定性,适合于现场应用。

目的比较间日疟原虫感染人群的Toll样受体(Toll-like receptor, TLR)5、TLR9基因3个单核苷酸多态性(single nucleotide polymorphism, SNP)位点差异,探讨其与间日疟原虫不同感染类型的相关性。方法收集中缅边境地区(云南省盈江县和缅甸拉咱市)2017—2019年间日疟原虫感染者202例及健康对照者104例,将上述研究对象分为无症状感染组、有症状感染组及健康对照组,其中无症状感染组与有症状感染组统称为感染组;采用飞行时间质谱分型技术检测以上研究对象TLR5、TLR9基因3个SNP位点,分析不同组之间TLR5、TLR9基因SNP位点等位基因和基因型的分布差异。结果 3组研究对象之间性别与年龄分布差异均无统计学意义(P均> 0.05);3组之间TLR9 1486C/T位点、TLR9 G1174A位点和TLR5 R392Stop位点的等位基因分布差异均无统计学意义(P均> 0.05);健康对照组与感染组间及健康对照组与无症状感染组间TLR9 1486C/T位点的AG基因型分布差异均有显著性统计学意义(P均 0.05)。结论 TLR9 1486C/T位点的基因型多态性与间日疟原虫感染相关,但尚未发现TLR9 G1174A位点、TLR5 R392Stop位点与间日疟原虫感染的相关性,本研究结果可为揭示宿主基因多态性对间日疟原虫感染的影响提供重要线索。

Background Understanding the genetic structure of natural populations provides insight into the demographic and adaptive processes that have affected those populations. Such information, particularly when integrated with geospatial data, can have translational applications for a variety of fields, including public health. Estimated effective migration surfaces (EEMS) is an approach that allows visualization of the spatial patterns in genomic data to understand population structure and migration. In this study, we developed a workflow to optimize the resolution of spatial grids used to generate EEMS migration maps and applied this optimized workflow to estimate migration of Plasmodium falciparum in Cambodia and bordering regions of Thailand and Vietnam. Methods The optimal density of EEMS grids was determined based on a new workflow created using density clustering to define genomic clusters and the spatial distance between genomic clusters. Topological skeletons were used to capture the spatial distribution for each genomic cluster and to determine the EEMS grid density; i.e., both genomic and spatial clustering were used to guide the optimization of EEMS grids. Model accuracy for migration estimates using the optimized workflow was tested and compared to grid resolutions selected without the optimized workflow. As a test case, the optimized workflow was applied to genomic data generated from P. falciparum sampled in Cambodia and bordering regions, and migration maps were compared to estimates of malaria endemicity, as well as geographic properties of the study area, as a means of validating observed migration patterns. Results Optimized grids displayed both high model accuracy and reduced computing time compared to grid densities selected in an unguided manner. In addition, EEMS migration maps generated for P. falciparum using the optimized grid corresponded to estimates of malaria endemicity and geographic properties of the study region that might be expected to impact malaria parasite migration, supporting the validity of the observed migration patterns. Conclusions Optimized grids reduce spatial uncertainty in the EEMS contours that can result from user-defined parameters, such as the resolution of the spatial grid used in the model. This workflow will be useful to a broad range of EEMS users as it can be applied to analyses involving other organisms of interest and geographic areas.

Vaccines based on Plasmodium falciparum apical membrane antigen 1 (AMA1) have failed due to extensive polymorphism in AMA1. To assess the strain-specificity of antibody responses to malaria infection and AMA1 vaccination, we designed protein and peptide microarrays representing hundreds of unique AMA1 variants. Following clinical malaria episodes, children had short-lived, sequence-independent increases in average whole-protein seroreactivity, as well as strain-specific responses to peptides representing diverse epitopes. Vaccination resulted in dramatically increased seroreactivity to all 263 AMA1 whole-protein variants. High-density peptide analysis revealed that vaccinated children had increases in seroreactivity to four distinct epitopes that exceeded responses to natural infection. A single amino acid change was critical to seroreactivity to peptides in a region of AMA1 associated with strain-specific vaccine efficacy. Antibody measurements using whole antigens may be biased towards conserved, immunodominant epitopes. Peptide microarrays may help to identify immunogenic epitopes, define correlates of vaccine protection, and measure strain-specific vaccine-induced antibodies.

摘要： 目的 比较3种不同检测方法对疟疾无症状感染者的检出能力,并了解中缅边境地区的疟疾无症状感染水平。方法 2014年7月在中缅边境地区云南省盈江县选择那邦镇、支那乡和缅甸拉咱安置点等3个调查点,采集调查对象血样,制作厚薄血膜和滤纸血标本,分别采用显微镜观察、荧光定量PCR和超敏PCR检测其疟原虫感染情况。结果 共采集387例血样,显微镜观察检出6例无症状感染者(间日疟5例、恶性疟1例),感染检出率为1.6%;荧光定量PCR检出13例无症状感染者(间日疟12例、恶性疟1例),感染检出率为3.4%;超敏PCR检出38例无症状感染者(间日疟29例、恶性疟9例),感染检出率为9.8%。以显微镜观察为疟原虫感染诊断的金标准,荧光定量PCR检测无症状感染者的灵敏度为100%,特异性为98.2%;超敏PCR检测无症状感染者的灵敏度为100%,特异性91.6%。超敏PCR结果显示,那邦镇的无症状感染检出率最高,为17.1%(22/129),其次为缅甸拉咱难民安置点,为10.0%(11/110),支那乡最低,为3.4%(5/148),3个调查点的感染检出率差异统计学意义(P0.05)。不同年龄组以15～29岁的无症状感染检出率最高,为17.5%(10/57),各年龄组间差异无统计学意义(P>0.05)。结论采用超敏PCR对疟疾无症状感染者的检出率高于荧光定量PCR和显微镜观察。中缅边境地区人群中存在一定比例的疟疾无症状感染者。

摘要： 疟疾无症状感染者在疟疾传播中具有重要作用,掌握其流行病学特征对实现消除疟疾目标具有重要的公共卫生意义。现有研究认为,无症状感染者分布广泛,在不同季节、不同传播水平地区以及任何年龄段均可发生,且受宿主、疟原虫、环境和传播媒介等多个方面的影响。本文综述了疟疾无症状感染者的定义、流行病学特征及其影响因素,为消除疟疾提供参考资料。