malaria diagnosis

疟疾诊断
  • 文章类型: Journal Article
    背景:准确的诊断和及时的治疗对于抗击疟疾至关重要。
    方法:用专家显微镜对449份样本进行恶性疟原虫感染筛查,qPCR,和三个RDT,即RapigenBiocredit疟疾AgPf(在单独的波段上检测HRP2和PLDH),雅培NxTek消除疟疾AgPf(检测HRP2),和SDBioline疟疾AgPf(检测HRP2)。通过数字PCR进行hrp2/3缺失分型。
    结果:45.7%(205/449)的个体通过qPCR检测为恶性疟原虫阳性,平均寄生虫密度为12.5寄生虫/μL。使用qPCR作为参考,显微镜的灵敏度为28.3%(58/205),生物信贷RDT为52.2%(107/205),NxTekRDT为49.3%(101/205),BiolineRDT为39.5%(81/205)。当仅包括密度>20个寄生虫/μL的样品时(n=89),显微镜检测灵敏度为62.9%(56/89),生物信贷88.8%(79/89),NxTek的88.8%(79/89),Bioline获得了78.7%(70/89)。所有三个RDT表现出>95%的特异性。检测限(样本检测呈阳性的概率为95%)为4393寄生虫/μL(显微镜检查),56种寄生虫/μL(生物信贷,考虑HRP2或pLDH),84寄生虫/μL(NxTek),和331种寄生虫/μL(Bioline)。三个qPCR证实的恶性疟原虫阳性样本均无,仅通过pLDH靶标鉴定,或所有RDT阴性但qPCR阳性的8个样品在>20寄生虫/μL的密度下携带hrp2/3缺失。
    结论:Biocredit和NxTekRDT显示出相当的诊断效果。所有三个RDT的表现均优于显微镜。
    BACKGROUND: Accurate diagnosis and timely treatment are crucial in combating malaria.
    METHODS: A total of 449 samples were screened for Plasmodium falciparum infection by expert microscopy, qPCR, and three RDTs, namely Rapigen Biocredit Malaria Ag Pf (detecting HRP2 and pLDH on separate bands), Abbott NxTek Eliminate Malaria Ag Pf (detecting HRP2), and SD Bioline Malaria Ag Pf (detecting HRP2). hrp2/3 deletion typing was done by digital PCR.
    RESULTS: 45.7% (205/449) individuals tested positive by qPCR for P. falciparum with a mean parasite density of 12.5 parasites/μL. Using qPCR as reference, the sensitivity of microscopy was 28.3% (58/205), the Biocredit RDT was 52.2% (107/205), the NxTek RDT was 49.3% (101/205), and the Bioline RDT was 39.5% (81/205). When only samples with densities > 20 parasites/μL were included (n = 89), sensitivity of 62.9% (56/89) by microscopy, 88.8% (79/89) by Biocredit, 88.8% (79/89) by NxTek, and 78.7% (70/89) by Bioline were obtained. All three RDTs demonstrated specificities > 95%. The limits of detection (95% probability that a sample tested positive) was 4393 parasites/μL (microscopy), 56 parasites/μL (Biocredit, considering either HRP2 or pLDH), 84 parasites/μL (NxTek), and 331 parasites/μL (Bioline). None of the three qPCR-confirmed P. falciparum positive samples, identified solely through the pLDH target, or eight samples negative for all RDTs but qPCR-positive at densities > 20 parasites/µL carried hrp2/3 deletions.
    CONCLUSIONS: The Biocredit and NxTek RDTs demonstrated comparable diagnostic efficacies. All three RDTs performed better than microscopy.
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  • 文章类型: Journal Article
    妊娠中的疟疾会导致不良后果,及时准确的诊断对于病例管理至关重要。在疟疾流行的国家,诊断主要基于快速诊断测试(RDT)和显微镜检查。然而,由低寄生虫血症和pfhrp2/3缺失引起的假阴性报告的增加引起人们对基于HRP2的RDT有效性的担忧.这项研究旨在评估RDT和显微镜性能,并描述布基纳法索418名孕妇队列中的pfhrp2/3缺失。使用RDT和显微镜检查诊断疟疾,并在产前护理访问期间收集血液样本。将诊断结果与PCR作为金标准进行比较。Pfhrp2和pfhrp3缺失的特征在于具有确诊的恶性疟原虫感染的患者。与显微镜检查相比,RDT具有更好的灵敏度(76%),但特异性(83%)较低(灵敏度=57%;特异性=98%)。低寄生虫血症(<150个寄生虫/微升),尤其是在多胎科中,是两种方法导致假阴性的主要因素。此外,在RDT的总体假阴性中,pfhrp2缺失频率为21.43%。在所有样本中发现较高的缺失频率,独立于RDT结果,例如,约2%的样本有双重缺失,这意味着大部分缺失对RDT检测没有影响.最后,在妊娠早期子宫高度较低的女性中发现pfhrp2缺失较高。建议在孕妇和布基纳法索进行更广泛和全国性的缺失监测研究。
    Malaria in pregnancy causes adverse consequences and prompt and accurate diagnosis is essential for case management. In malaria endemic countries, diagnosis is mainly based on rapid diagnostic tests (RDT) and microscopy. However, increasing reports of false negatives caused by low parasitemia and pfhrp2/3 deletions raise concerns about HRP2-based RDT usefulness. This study aimed to assess RDT and microscopy performance and to describe pfhrp2/3 deletions in a cohort of 418 pregnant women in Burkina Faso. Malaria was diagnosed using RDT and microscopy and blood samples were collected during antenatal care visits. Diagnostic results were compared to PCR as gold standard. Pfhrp2 and pfhrp3 deletions were characterized for patients with confirmed P. falciparum infection. RDT had better sensitivity (76%) but lower specificity (83%) than microscopy (sensitivity = 57%; specificity = 98%). Low parasitemia (<150 parasites/µL), especially in multigravidae, was the principal factor causing false negatives by both methods. Moreover, pfhrp2 deletion frequency among overall false negatives by RDT was 21.43%. Higher frequency of deletions was found among all samples, independently of RDT result, for example around 2% of samples had double deletions meaning that the majority of deletions had no effect on RDT testing. Finally, it was found higher pfhrp2 deletion in women with lower uterine height during the first trimester. Wider and National surveillance study of deletions is recommended among pregnant women and in Burkina Faso.
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  • 文章类型: Journal Article
    数字显微镜的改进对于开发在细胞水平上准确并表现出令人满意的临床表现的疟疾诊断方法至关重要。数字显微镜可以通过改进深度学习算法和实现一致的染色结果来增强。在这项研究中,提出了一种新型的miLab™设备,该设备采用了固体水凝胶染色方法,用于一致的血膜制备,省去了使用复杂的设备和液体试剂的维护。miLab™确保一致,高品质,通过利用可变形的染色片,在各种血细胞比容上可复制的血膜。嵌入式深度学习功能的miLab™用于使用内部光学系统从染色的血细胞的自动聚焦图像中检测和分类疟疾寄生虫。该方法的结果与手动显微镜图像一致。这种方法不仅最大限度地减少了人为错误,而且还有助于远程协助和专家通过数字图像传输进行审查。该方法可以为现场疟疾诊断树立新的范式。用于疟疾检测的miLab™算法对于感染的红细胞(RBC)分类实现了98.86%的总准确度。在马拉维进行的临床验证显示了92.21%的总体百分比一致性。基于这些结果,miLab™可以成为分散式疟疾诊断的可靠高效工具。
    Improvements in digital microscopy are critical for the development of a malaria diagnosis method that is accurate at the cellular level and exhibits satisfactory clinical performance. Digital microscopy can be enhanced by improving deep learning algorithms and achieving consistent staining results. In this study, a novel miLab™ device incorporating the solid hydrogel staining method was proposed for consistent blood film preparation, eliminating the use of complex equipment and liquid reagent maintenance. The miLab™ ensures consistent, high-quality, and reproducible blood films across various hematocrits by leveraging deformable staining patches. Embedded-deep-learning-enabled miLab™ was utilized to detect and classify malarial parasites from autofocused images of stained blood cells using an internal optical system. The results of this method were consistent with manual microscopy images. This method not only minimizes human error but also facilitates remote assistance and review by experts through digital image transmission. This method can set a new paradigm for on-site malaria diagnosis. The miLab™ algorithm for malaria detection achieved a total accuracy of 98.86% for infected red blood cell (RBC) classification. Clinical validation performed in Malawi demonstrated an overall percent agreement of 92.21%. Based on these results, miLab™ can become a reliable and efficient tool for decentralized malaria diagnosis.
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  • 文章类型: Case Reports
    及时诊断疟疾感染对于有效管理至关重要,然而,由于不同的潜伏期和需要医生发起的实验室检查,这可能是具有挑战性的.我们介绍了一个40岁的男性发烧和深色尿液的病例,最初评估败血症。在获得疟疾流行地区的远程旅行史后,在外周涂片检查中偶然发现了间日疟原虫。与疾病控制中心的协商证实了诊断,强调对疟疾疑似病例进行全面旅行史评估和及时实验室调查的重要性。此病例强调了早期诊断在管理这种潜在威胁生命的感染中的重要性。
    Prompt diagnosis of malaria infection is critical for effective management, yet it can be challenging due to varying incubation periods and the need for physician-initiated laboratory workups. We present a case of a 40-year-old male with fever and dark-colored urine, initially evaluated for sepsis. Plasmodium vivax was incidentally identified on a peripheral smear review after obtaining a remote travel history from a malaria-endemic area. Consultation with the Centers for Disease Control confirmed the diagnosis, emphasizing the importance of thorough travel history assessment and timely laboratory investigation in suspected cases of malaria. This case underscores the significance of early diagnosis in managing this potentially life-threatening infection.
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  • 文章类型: Journal Article
    疟疾是全球重大的健康问题,特别是在非洲,其患病率仍然高得惊人。使用人工智能算法诊断疟疾细胞为临床医生提供了极大的便利。在本文中,提出了一种用于疟疾疾病诊断的密集连通卷积动态学习网络(DCDLN)。具体来说,在对数据集进行数据处理和分区之后,密集连接块被训练为特征提取器。要对特征提取器提取的特征进行分类,本文提出了一种基于动态学习网络的分类器。根据实验结果,提出的DCDLN方法的诊断准确率为97.23%,在开放的疟疾细胞数据集上,超过了现有的先进方法的诊断性能。这种准确的诊断效果为临床医生做出正确的诊断提供了令人信服的证据。此外,为了验证DCDLN算法的优越性和泛化能力,我们还将该算法应用于皮肤癌和垃圾分类数据集。DCDLN在这些数据集上也取得了良好的结果,证明了DCDLN算法具有优越性和较强的泛化性能。
    Malaria is a significant health concern worldwide, particularly in Africa where its prevalence is still alarmingly high. Using artificial intelligence algorithms to diagnose cells with malaria provides great convenience for clinicians. In this paper, a densely connected convolutional dynamic learning network (DCDLN) is proposed for the diagnosis of malaria disease. Specifically, after data processing and partitioning of the dataset, the densely connected block is trained as a feature extractor. To classify the features extracted by the feature extractor, a classifier based on a dynamic learning network is proposed in this paper. Based on experimental results, the proposed DCDLN method demonstrates a diagnostic accuracy rate of 97.23%, surpassing the diagnostic performance than existing advanced methods on an open malaria cell dataset. This accurate diagnostic effect provides convincing evidence for clinicians to make a correct diagnosis. In addition, to validate the superiority and generalization capability of the DCDLN algorithm, we also applied the algorithm to the skin cancer and garbage classification datasets. DCDLN achieved good results on these datasets as well, demonstrating that the DCDLN algorithm possesses superiority and strong generalization performance.
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  • 文章类型: Case Reports
    经过两周的哈萨克斯坦之行,一名42岁的妇女因发烧出现在德国急诊室,头痛,恶心,神经症状。迅速诊断出恶性疟原虫感染。患者立即接受静脉注射青蒿琥酯治疗,并转移到重症监护病房。最初的寄生虫密度高达30%感染的红细胞与845880寄生虫/μL。自2012年哈萨克斯坦宣布无疟疾以来,已经开始对疟原虫进行分子检测,以确定可能的来源。msp-1基因和微卫星标记的基因分型表明,这些寄生虫起源于非洲,具有两个不同的等位基因,表明多克隆感染。住院10天后,病人身体健康出院。总的来说,我们的研究结果强调,疟疾必须列入不明原因发热患者的鉴别诊断清单,即使他们来自疟疾不常见的国家。
    Following a 2-week trip to Kazakhstan, a 42-year-old woman presented at the emergency department in Germany with fever, headache, nausea, and neurological symptoms. An infection with Plasmodium falciparum was rapidly diagnosed. The patient was immediately treated with intravenous artesunate and transferred to an intensive care unit. The initial parasite density was as high as 30% infected erythrocytes with 845,880 parasites/µL. Since Kazakhstan was declared malaria-free in 2012, molecular testing for Plasmodium has been initiated to identify a possible origin. Genotyping of the msp-1 gene and microsatellite markers showed that the parasites are of African origin, with two different alleles indicating a polyclonal infection. After a hospitalization of 10 days, the patient was discharged in good health. Overall, our results emphasize that malaria must be on the list of differential diagnoses for patients with fever of unknown origin, even if they come from countries where malaria does not commonly occur.
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  • 文章类型: Journal Article
    疟疾是撒哈拉以南非洲最普遍的传染病之一,根据世界卫生组织的数据,2021年全球报告了2.47亿病例。光学显微镜仍然是疟疾诊断的黄金标准技术,然而,它需要专业知识,既耗时又难以复制。因此,基于使用人工智能工具的数字图像分析的新诊断技术可以改善诊断并帮助自动化诊断。
    在这项研究中,创建了2571张标记的厚血涂片图像的数据集.YOLOv5x,更快的R-CNN,SSD,和RetinaNet对象检测神经网络在相同的数据集上进行训练,以评估它们在疟原虫寄生虫检测中的性能。应用注意力模块并与YOLOv5x结果进行比较。要使整个诊断过程自动化,3D打印件的原型被设计用于传统光学显微镜的机器人化,能够自动聚焦样品和跟踪整个幻灯片。
    比较分析得出YOLOv5x在精度为92.10%的测试集上的性能,93.50%召回,92.79%F分数,和94.40%mAP0.5的白细胞,早期和成熟的疟原虫滋养体整体检测。白细胞各分类的F-得分值为99.0%,早期滋养体检测为88.6%,成熟滋养体检测为87.3%。与YOLOv5x原始训练模型相比,注意力模块的性能表现出无显着的统计差异。预测模型被集成到智能手机计算机应用程序中,用于实验室中基于图像的诊断。该系统可以通过机器人显微镜的自动对焦和X-Y运动来执行全自动诊断,为数字图像分析而训练的CNN模型,和智能手机设备。新的原型将确定Giemsa染色的厚血涂片样本对疟原虫感染及其寄生虫水平是否为阳性/阴性。整个系统已集成到iMAGING智能手机应用程序中。
    通过自动对焦和滑动运动实现全自动系统的合并,并通过智能手机软件和AI算法自动检测数字图像中的疟原虫寄生虫,使原型具有最佳功能,可以加入全球抗击疟疾的努力。被忽视的热带病和其他传染病。
    UNASSIGNED: Malaria is one of the most prevalent infectious diseases in sub-Saharan Africa, with 247 million cases reported worldwide in 2021 according to the World Health Organization. Optical microscopy remains the gold standard technique for malaria diagnosis, however, it requires expertise, is time-consuming and difficult to reproduce. Therefore, new diagnostic techniques based on digital image analysis using artificial intelligence tools can improve diagnosis and help automate it.
    UNASSIGNED: In this study, a dataset of 2571 labeled thick blood smear images were created. YOLOv5x, Faster R-CNN, SSD, and RetinaNet object detection neural networks were trained on the same dataset to evaluate their performance in Plasmodium parasite detection. Attention modules were applied and compared with YOLOv5x results. To automate the entire diagnostic process, a prototype of 3D-printed pieces was designed for the robotization of conventional optical microscopy, capable of auto-focusing the sample and tracking the entire slide.
    UNASSIGNED: Comparative analysis yielded a performance for YOLOv5x on a test set of 92.10% precision, 93.50% recall, 92.79% F-score, and 94.40% mAP0.5 for leukocyte, early and mature Plasmodium trophozoites overall detection. F-score values of each category were 99.0% for leukocytes, 88.6% for early trophozoites and 87.3% for mature trophozoites detection. Attention modules performance show non-significant statistical differences when compared to YOLOv5x original trained model. The predictive models were integrated into a smartphone-computer application for the purpose of image-based diagnostics in the laboratory. The system can perform a fully automated diagnosis by the auto-focus and X-Y movements of the robotized microscope, the CNN models trained for digital image analysis, and the smartphone device. The new prototype would determine whether a Giemsa-stained thick blood smear sample is positive/negative for Plasmodium infection and its parasite levels. The whole system was integrated into the iMAGING smartphone application.
    UNASSIGNED: The coalescence of the fully-automated system via auto-focus and slide movements and the autonomous detection of Plasmodium parasites in digital images with a smartphone software and AI algorithms confers the prototype the optimal features to join the global effort against malaria, neglected tropical diseases and other infectious diseases.
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  • 文章类型: Journal Article
    由于血液样本的获取困难,这是目前用于检测疟原虫的侵入性方法。,需要有效且非侵入性的替代诊断采样方法,特别是长期研究。疟疾感染者的唾液和粪便样本含有痕量的疟原虫DNA,因此可以用作替代品。使用快速诊断测试筛查疟疾,并通过显微镜确认。对血液进行针对恶性疟原虫特异性STEVOR基因的巢式PCR测试,唾液和粪便样本对疟疾呈阳性。招募了三百六十七(367)名儿童,其中八十(22.22%)被确认为疟疾阳性。匹配的血液,有35名儿童的唾液和粪便样本。通过使用血液涂片作为诊断疟疾的黄金标准,我们的研究表明,与唾液(22.86%)和粪便(14.29%)相比,血液(100%)中的疟原虫DNA检测率更高.将qPCR应用于STEVOR基因以检测唾液和粪便样品中的恶性疟原虫DNA不能被认为是使用血液样本的当前疟疾检测过程的替代方法。
    Due to the difficulty of obtaining blood samples, which is the invasive method that is currently used for the detection of Plasmodium spp., alternative diagnostic sampling methods that are effective and non-invasive are needed, particularly for long-term studies. Saliva and stool samples from malaria-infected individuals contain trace amounts of Plasmodium DNA and therefore could be used as alternatives. Malaria was screened using rapid diagnosis tests and confirmed via microscopy. Nested PCR tests targeting the Plasmodium falciparum-specific STEVOR gene were performed for blood, saliva and stool samples that were positive for malaria. Three hundred sixty-seven (367) children were enrolled and eighty (22.22%) were confirmed to be positive for malaria. Matched blood, saliva and stool samples were available for 35 children. By using blood smears as the gold standard for the diagnosis of malaria, our study indicates that Plasmodium DNA was more detectable in blood (100%) than in saliva (22.86%) and stools (14.29%). Applying qPCR to the STEVOR gene to detect Plasmodium falciparum DNA in saliva and stool samples cannot be considered as an alternative to the current malaria detection processes using blood specimens.
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  • 文章类型: Preprint
    背景:准确的诊断和及时的治疗对于抗击疟疾至关重要。方法:我们评估了三种快速诊断测试(RDT)在诊断发热患者中的诊断性能,即:雅培NxTek消除疟疾AgPf(检测HRP2),RapigenBiocredit疟疾AgPf(在单独的波段上检测HRP2和LDH),和SDBioline疟疾AgPf(检测HRP2)。将结果与qPCR进行比较。结果:449例临床患者中,45.7%(205/449)通过qPCR检测为阳性的恶性疟原虫,平均寄生虫密度为12.5寄生虫/μL。生物信贷RDT的灵敏度为52.2%(107/205),NxTekRDT为49.3%(101/205),BiolineRDT为40.5%(83/205)。当寄生虫密度低于20寄生虫/uL的样品被排除(n=116),灵敏度为88.8%(79/89,NxTek),89.9%(80/89,生物信贷),获得78.7%(70/89,Bioline)。所有三种RDT表现出高于95%的特异性。检测限为84种寄生虫/μL(NxTek),56种寄生虫/μL(生物信贷,考虑HRP2或LDH),和331种寄生虫/μL(Bioline)。三个qPCR证实的恶性疟原虫阳性样本均无,仅通过LDH靶标鉴定,携带hrp2/3缺失。结论:Biocredit和NxTekRDT显示出可比的诊断功效,并且两种RDT的表现均优于BiolineRDT。
    UNASSIGNED: Accurate diagnosis and timely treatment are crucial in combating malaria.
    UNASSIGNED: We evaluated the diagnostic performance of three Rapid Diagnostic Tests (RDTs) in diagnosing febrile patients, namely: Abbott NxTek Eliminate Malaria Ag Pf (detecting HRP2), Rapigen Biocredit Malaria Ag Pf (detecting HRP2 and LDH on separate bands), and SD Bioline Malaria Ag Pf (detecting HRP2). Results were compared to qPCR.
    UNASSIGNED: Among 449 clinical patients, 45.7% (205/449) tested positive by qPCR for P. falciparum with a mean parasite density of 12.5parasites/μL. The sensitivity of the Biocredit RDT was 52.2% (107/205), NxTek RDT was 49.3% (101/205), and Bioline RDT was 40.5% (83/205). When samples with parasite densities lower than 20 parasites/uL were excluded (n=116), a sensitivity of 88.8% (79/89, NxTek), 89.9% (80/89, Biocredit), and 78.7% (70/89, Bioline) was obtained. All three RDTs demonstrated specificity above 95%. The limits of detection was 84 parasites/μL (NxTek), 56 parasites/μL (Biocredit, considering either HRP2 or LDH), and 331 parasites/μL (Bioline). None of the three qPCR-confirmed P. falciparum positive samples, identified solely through the LDH target, carried hrp2/3 deletions.
    UNASSIGNED: The Biocredit and NxTek RDTs demonstrated comparable diagnostic efficacies and both RDTs performed better than Bioline RDT.
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  • 文章类型: Journal Article
    疟疾是一个重大的公共卫生问题,95%的病例发生在非洲,但是在偏远和低收入地区,准确和及时的诊断是有问题的。这里,我们开发了一种基于人工智能的疟疾诊断对象检测系统(AIDMAN)。在这个系统中,YOLOv5模型用于检测薄血液涂片中的细胞。然后将注意对准器模型(AAM)应用于由多尺度特征组成的细胞分类,局部上下文对齐器,多尺度关注。最后,卷积神经网络分类器用于使用血液涂片图像进行诊断,减少假阳性细胞引起的干扰。结果表明,AIDMAN能很好地处理干扰,细胞的诊断准确率为98.62%,血液涂片图像的诊断准确率为97%。98.44%的前瞻性临床验证准确性与显微镜医师相当。AIDMAN显示了临床上可接受的疟疾寄生虫检测,可以帮助疟疾诊断,特别是在缺乏经验丰富的寄生虫学家和设备的地区。
    Malaria is a significant public health concern, with ∼95% of cases occurring in Africa, but accurate and timely diagnosis is problematic in remote and low-income areas. Here, we developed an artificial intelligence-based object detection system for malaria diagnosis (AIDMAN). In this system, the YOLOv5 model is used to detect cells in a thin blood smear. An attentional aligner model (AAM) is then applied for cellular classification that consists of multi-scale features, a local context aligner, and multi-scale attention. Finally, a convolutional neural network classifier is applied for diagnosis using blood-smear images, reducing interference caused by false positive cells. The results demonstrate that AIDMAN handles interference well, with a diagnostic accuracy of 98.62% for cells and 97% for blood-smear images. The prospective clinical validation accuracy of 98.44% is comparable to that of microscopists. AIDMAN shows clinically acceptable detection of malaria parasites and could aid malaria diagnosis, especially in areas lacking experienced parasitologists and equipment.
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