新发传染病检测和监控技术的研究进展
Research Progress on Detection and Monitoring Technologies for Emerging Infectious Diseases
摘要: 新发传染病是指新近出现或重新抬头的感染性疾病,其流行受人口增长、气候变化、全球化旅行及宿主免疫状态等多因素驱动。本文系统综述了新发传染病病原体检测与监控技术的研究进展,重点阐释了分子诊断技术的革新及其在疫情防控中的关键作用。传统病原体鉴定方法(如培养分离、血清学检测)虽具价值,但存在灵敏度低、耗时长等局限。聚合酶链反应(PCR)及新一代测序(NGS)技术的突破,显著提升了病原体发现的效率与准确性:从基于序列非依赖性扩增的病毒发现(如HHV-8、MCPyV),到宏基因组学在无偏倚病原体筛查中的应用(如SARS-CoV-2的快速鉴定)。此外,生物信息学与“全健康”(One Health)策略的整合,为跨物种传播风险预警提供了新范式。未来,高通量测序技术、人工智能辅助诊断及全球化监测网络的协同发展,将进一步提升新发传染病的早期识别与应对能力。
Abstract: Emerging infectious diseases (EIDs), defined as newly identified or re-emerging infections, are fueled by factors including population growth, climate change, global travel, and host immune status. This review comprehensively summarizes advances in pathogen detection and surveillance technologies, emphasizing the transformative role of molecular diagnostics. While conventional methods (e.g., culture isolation, serology) remain foundational, their limitations in sensitivity and turnaround time have been addressed by breakthroughs in polymerase chain reaction (PCR) and next-generation sequencing (NGS). Key milestones range from sequence-independent amplification techniques (e.g., discovery of HHV-8 and MCPyV) to metagenomics for unbiased pathogen screening (e.g., rapid identification of SARS-CoV-2). Integration of bioinformatics and the “One Health” framework has further enabled early warning of cross-species transmission risks. Future directions include high-throughput sequencing, AI-assisted diagnostics, and global surveillance networks to enhance preparedness against EIDs.
文章引用:谢蕴涵, 吴亮. 新发传染病检测和监控技术的研究进展[J]. 临床个性化医学, 2025, 4(4): 158-168. https://doi.org/10.12677/jcpm.2025.44430

参考文献

[1] Morens, D.M., Folkers, G.K. and Fauci, A.S. (2004) The Challenge of Emerging and Re-Emerging Infectious Diseases. Nature, 430, 242-249. [Google Scholar] [CrossRef] [PubMed]
[2] Morse, S.S. (1995) Factors in the Emergence of Infectious Diseases. Emerging Infectious Diseases, 1, 7-15. [Google Scholar] [CrossRef] [PubMed]
[3] Jacobsen, K. and Koopman, J. (2005) The Effects of Socioeconomic Development on Worldwide Hepatitis a Virus Seroprevalence Patterns. International Journal of Epidemiology, 34, 600-609. [Google Scholar] [CrossRef] [PubMed]
[4] Panagiotopoulos, T., Antoniadou, I., Valassi-Adam, E. and Berger, A. (1999) Increase in Congenital Rubella Occurrence after Immunisation in Greece: Retrospective Survey and Systematic Review How Does Herd Immunity Work? BMJ, 319, 1462-1467. [Google Scholar] [CrossRef] [PubMed]
[5] Coombes, R. (2017) Europe Steps up Action against Vaccine Hesitancy as Measles Outbreaks Continue. BMJ, 359, j4803. [Google Scholar] [CrossRef] [PubMed]
[6] Lo, N.C. and Hotez, P.J. (2017) Public Health and Economic Consequences of Vaccine Hesitancy for Measles in the United States. JAMA Pediatrics, 171, 887-892. [Google Scholar] [CrossRef] [PubMed]
[7] Baur, D., Gladstone, B.P., Burkert, F., Carrara, E., Foschi, F., Döbele, S., et al. (2017) Effect of Antibiotic Stewardship on the Incidence of Infection and Colonisation with Antibiotic-Resistant Bacteria and Clostridium Difficile Infection: A Systematic Review and Meta-Analysis. The Lancet Infectious Diseases, 17, 990-1001. [Google Scholar] [CrossRef] [PubMed]
[8] Byrd, A.L. and Segre, J.A. (2016) Adapting Koch’s Postulates. Science, 351, 224-226. [Google Scholar] [CrossRef] [PubMed]
[9] Falkow, S. (2004) Molecular Koch’s Postulates Applied to Bacterial Pathogenicity—A Personal Recollection 15 Years Later. Nature Reviews Microbiology, 2, 67-72. [Google Scholar] [CrossRef] [PubMed]
[10] O’Connor, S.M., Taylor, C.E. and Hughes, J.M. (2006) Emerging Infectious Determinants of Chronic Diseases. Emerging Infectious Diseases, 12, 1051-1057. [Google Scholar] [CrossRef] [PubMed]
[11] Falkow, S. (1988) Molecular Koch’s Postulates Applied to Microbial Pathogenicity. Clinical Infectious Diseases, 10, S274-S276. [Google Scholar] [CrossRef] [PubMed]
[12] Nicolás, I., Marimon, L., Barnadas, E., Saco, A., Rodríguez-Carunchio, L., Fusté, P., et al. (2019) HPV-Negative Tumors of the Uterine Cervix. Modern Pathology, 32, 1189-1196. [Google Scholar] [CrossRef] [PubMed]
[13] Mesri, E.A., Feitelson, M.A. and Munger, K. (2014) Human Viral Oncogenesis: A Cancer Hallmarks Analysis. Cell Host & Microbe, 15, 266-282. [Google Scholar] [CrossRef] [PubMed]
[14] Choi, I.J., Kook, M., Kim, Y., Cho, S., Lee, J.Y., Kim, C.G., et al. (2018) Helicobacter pylori Therapy for the Prevention of Metachronous Gastric Cancer. New England Journal of Medicine, 378, 1085-1095. [Google Scholar] [CrossRef] [PubMed]
[15] Karczewski, K.J. and Snyder, M.P. (2018) Integrative Omics for Health and Disease. Nature Reviews Genetics, 19, 299-310. [Google Scholar] [CrossRef] [PubMed]
[16] Blevins, S.M. and Bronze, M.S. (2010) Robert Koch and the ‘Golden Age’ of Bacteriology. International Journal of Infectious Diseases, 14, e744-e751. [Google Scholar] [CrossRef] [PubMed]
[17] Pasteur, L. (1881) On the Germ Theory. Science, 2, 420-422. [Google Scholar] [CrossRef
[18] Lwoff, A. (1957) The Concept of Virus. Microbiology, 17, 239-253. [Google Scholar] [CrossRef] [PubMed]
[19] Leland, D.S. and Ginocchio, C.C. (2007) Role of Cell Culture for Virus Detection in the Age of Technology. Clinical Microbiology Reviews, 20, 49-78. [Google Scholar] [CrossRef] [PubMed]
[20] Doern, G.V. (2000) Detection of Selected Fastidious Bacteria. Clinical Infectious Diseases, 30, 166-173. [Google Scholar] [CrossRef] [PubMed]
[21] Curry, A., Appleton, H. and Dowsett, B. (2006) Application of Transmission Electron Microscopy to the Clinical Study of Viral and Bacterial Infections: Present and Future. Micron, 37, 91-106. [Google Scholar] [CrossRef] [PubMed]
[22] Gocke, D.J. and Howe, C. (1970) Rapid Detection of Australia Antigen by Counterimmunoelectrophoresis. The Journal of Immunology, 104, 1031-1032. [Google Scholar] [CrossRef
[23] Stanford, J.L. (1973) Immunodiffusion Analysis—A Rational Basis for the Taxonomy of Mycobacteria. Annales de la Société Belge de Médecine Tropicale, 53, 321-330.
[24] Larremore, D.B., Fosdick, B.K., Bubar, K.M., Zhang, S., Kissler, S.M., Metcalf, C.J.E., et al. (2021) Estimating SARS-CoV-2 Seroprevalence and Epidemiological Parameters with Uncertainty from Serological Surveys. eLife, 10, e64206. [Google Scholar] [CrossRef] [PubMed]
[25] Lipkin, W.I. and Firth, C. (2013) Viral Surveillance and Discovery. Current Opinion in Virology, 3, 199-204. [Google Scholar] [CrossRef] [PubMed]
[26] Mullis, K.B. (1990) The Unusual Origin of the Polymerase Chain Reaction. Scientific American, 262, 56-65. [Google Scholar] [CrossRef] [PubMed]
[27] Li, J. and Macdonald, J. (2015) Advances in Isothermal Amplification: Novel Strategies Inspired by Biological Processes. Biosensors and Bioelectronics, 64, 196-211. [Google Scholar] [CrossRef] [PubMed]
[28] Allander, T., Tammi, M.T., Eriksson, M., Bjerkner, A., Tiveljung-Lindell, A. and Andersson, B. (2005) Cloning of a Human Parvovirus by Molecular Screening of Respiratory Tract Samples. Proceedings of the National Academy of Sciences of the United States of America, 102, 12891-12896. [Google Scholar] [CrossRef] [PubMed]
[29] Greub, G., Sahli, R., Brouillet, R. and Jaton, K. (2016) Ten Years of R&D and Full Automation in Molecular Diagnosis. Future Microbiology, 11, 403-425. [Google Scholar] [CrossRef] [PubMed]
[30] Vermeulen, M., Lelie, N., Sykes, W., Crookes, R., Swanevelder, J., Gaggia, L., et al. (2009) Impact of Individual‐Donation Nucleic Acid Testing on Risk of Human Immunodeficiency Virus, Hepatitis B Virus, and Hepatitis C Virus Transmission by Blood Transfusion in South Africa. Transfusion, 49, 1115-1125. [Google Scholar] [CrossRef] [PubMed]
[31] Gorzalski, A.J., Tian, H., Laverdure, C., Morzunov, S., Verma, S.C., VanHooser, S., et al. (2020) High-Throughput Transcription-Mediated Amplification on the Hologic Panther Is a Highly Sensitive Method of Detection for SARS-CoV-2. Journal of Clinical Virology, 129, Article ID: 104501. [Google Scholar] [CrossRef] [PubMed]
[32] Opota, O., Brouillet, R., Greub, G. and Jaton, K. (2020) Comparison of SARS-CoV-2 RT-PCR on a High-Throughput Molecular Diagnostic Platform and the Cobas SARS-CoV-2 Test for the Diagnostic of COVID-19 on Various Clinical Samples. Pathogens and Disease, 78, ftaa061. [Google Scholar] [CrossRef] [PubMed]
[33] Raftery, P., Condell, O., Wasunna, C., Kpaka, J., Zwizwai, R., Nuha, M., et al. (2018) Establishing Ebola Virus Disease (EVD) Diagnostics Using Genexpert Technology at a Mobile Laboratory in Liberia: Impact on Outbreak Response, Case Management and Laboratory Systems Strengthening. PLOS Neglected Tropical Diseases, 12, e0006135. [Google Scholar] [CrossRef] [PubMed]
[34] Zhen, W., Smith, E., Manji, R., Schron, D. and Berry, G.J. (2020) Clinical Evaluation of Three Sample-To-Answer Platforms for Detection of SARS-CoV-2. Journal of Clinical Microbiology, 58, e00783-20. [Google Scholar] [CrossRef] [PubMed]
[35] Lisitsyn, N., Lisitsyn, N. and Wigler, M. (1993) Cloning the Differences between Two Complex Genomes. Science, 259, 946-951. [Google Scholar] [CrossRef] [PubMed]
[36] Chang, Y., Cesarman, E., Pessin, M.S., Lee, F., Culpepper, J., Knowles, D.M., et al. (1994) Identification of Herpesvirus-Like DNA Sequences in Aids-Sssociated Kaposi’s Sarcoma. Science, 266, 1865-1869. [Google Scholar] [CrossRef] [PubMed]
[37] Scheinberg, I.H. (1979) Thrombocytopenic Reaction to Aspirin and Acetaminophen. The New England Journal of Medicine, 300, 678.
[38] Cesarman, E., Chang, Y., Moore, P.S., Said, J.W. and Knowles, D.M. (1995) Kaposi’s Sarcoma-Associated Herpesvirus-Like DNA Sequences in Aids-Related Body-Cavity-Based Lymphomas. New England Journal of Medicine, 332, 1186-1191. [Google Scholar] [CrossRef] [PubMed]
[39] Simons, J.N., Pilot-Matias, T.J., Leary, T.P., Dawson, G.J., Desai, S.M., Schlauder, G.G., et al. (1995) Identification of Two Flavivirus-Like Genomes in the GB Hepatitis Agent. Proceedings of the National Academy of Sciences of the United States of America, 92, 3401-3405. [Google Scholar] [CrossRef] [PubMed]
[40] Nishizawa, T., Okamoto, H., Konishi, K., Yoshizawa, H., Miyakawa, Y. and Mayumi, M. (1997) A Novel DNA Virus (TTV) Associated with Elevated Transaminase Levels in Posttransfusion Hepatitis of Unknown Etiology. Biochemical and Biophysical Research Communications, 241, 92-97. [Google Scholar] [CrossRef] [PubMed]
[41] Jones, M.S., Kapoor, A., Lukashov, V.V., Simmonds, P., Hecht, F. and Delwart, E. (2005) New DNA Viruses Identified in Patients with Acute Viral Infection Syndrome. Journal of Virology, 79, 8230-8236. [Google Scholar] [CrossRef] [PubMed]
[42] van der Hoek, L., Pyrc, K., Jebbink, M.F., Vermeulen-Oost, W., Berkhout, R.J.M., Wolthers, K.C., et al. (2004) Identification of a New Human Coronavirus. Nature Medicine, 10, 368-373. [Google Scholar] [CrossRef] [PubMed]
[43] Maxam, A.M. and Gilbert, W. (1977) A New Method for Sequencing DNA. Proceedings of the National Academy of Sciences of the United States of America, 74, 560-564. [Google Scholar] [CrossRef] [PubMed]
[44] Sanger, F., Nicklen, S. and Coulson, A.R. (1977) DNA Sequencing with Chain-Terminating Inhibitors. Proceedings of the National Academy of Sciences of the United States of America, 74, 5463-5467. [Google Scholar] [CrossRef] [PubMed]
[45] Prober, J.M., Trainor, G.L., Dam, R.J., Hobbs, F.W., Robertson, C.W., Zagursky, R.J., et al. (1987) A System for Rapid DNA Sequencing with Fluorescent Chain-Terminating Dideoxynucleotides. Science, 238, 336-341. [Google Scholar] [CrossRef] [PubMed]
[46] van Dijk, E.L., Auger, H., Jaszczyszyn, Y. and Thermes, C. (2014) Ten Years of Next-Generation Sequencing Technology. Trends in Genetics, 30, 418-426. [Google Scholar] [CrossRef] [PubMed]
[47] von Bubnoff, A. (2008) Next-Generation Sequencing: The Race Is On. Cell, 132, 721-723. [Google Scholar] [CrossRef] [PubMed]
[48] Feng, H., Shuda, M., Chang, Y. and Moore, P.S. (2008) Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma. Science, 319, 1096-1100. [Google Scholar] [CrossRef] [PubMed]
[49] Marine, R., Polson, S.W., Ravel, J., Hatfull, G., Russell, D., Sullivan, M., et al. (2011) Evaluation of a Transposase Protocol for Rapid Generation of Shotgun High-Throughput Sequencing Libraries from Nanogram Quantities of DNA. Applied and Environmental Microbiology, 77, 8071-8079. [Google Scholar] [CrossRef] [PubMed]
[50] Palacios, G., Druce, J., Du, L., Tran, T., Birch, C., Briese, T., et al. (2008) A New Arenavirus in a Cluster of Fatal Transplant-Associated Diseases. New England Journal of Medicine, 358, 991-998. [Google Scholar] [CrossRef] [PubMed]
[51] Jerome, H., Taylor, C., Sreenu, V.B., Klymenko, T., Filipe, A.D.S., Jackson, C., et al. (2019) Metagenomic Next-Generation Sequencing Aids the Diagnosis of Viral Infections in Febrile Returning Travellers. Journal of Infection, 79, 383-388. [Google Scholar] [CrossRef] [PubMed]
[52] Graf, E.H., Simmon, K.E., Tardif, K.D., Hymas, W., Flygare, S., Eilbeck, K., et al. (2016) Unbiased Detection of Respiratory Viruses by Use of RNA Sequencing-Based Metagenomics: A Systematic Comparison to a Commercial PCR Panel. Journal of Clinical Microbiology, 54, 1000-1007. [Google Scholar] [CrossRef] [PubMed]
[53] Huang, B., Jennison, A., Whiley, D., McMahon, J., Hewitson, G., Graham, R., et al. (2019) Illumina Sequencing of Clinical Samples for Virus Detection in a Public Health Laboratory. Scientific Reports, 9, Article No. 5409. [Google Scholar] [CrossRef] [PubMed]
[54] Kustin, T., Ling, G., Sharabi, S., Ram, D., Friedman, N., Zuckerman, N., et al. (2019) A Method to Identify Respiratory Virus Infections in Clinical Samples Using Next-Generation Sequencing. Scientific Reports, 9, Article No. 2606. [Google Scholar] [CrossRef] [PubMed]
[55] O’Flaherty, B.M., Li, Y., Tao, Y., Paden, C.R., Queen, K., Zhang, J., et al. (2018) Comprehensive Viral Enrichment Enables Sensitive Respiratory Virus Genomic Identification and Analysis by Next Generation Sequencing. Genome Research, 28, 869-877. [Google Scholar] [CrossRef] [PubMed]
[56] Wylie, T.N., Wylie, K.M., Herter, B.N. and Storch, G.A. (2015) Enhanced Virome Sequencing Using Targeted Sequence Capture. Genome Research, 25, 1910-1920. [Google Scholar] [CrossRef] [PubMed]
[57] Wylie, K.M., Wylie, T.N., Buller, R., Herter, B., Cannella, M.T. and Storch, G.A. (2018) Detection of Viruses in Clinical Samples by Use of Metagenomic Sequencing and Targeted Sequence Capture. Journal of Clinical Microbiology, 56, e01123-18. [Google Scholar] [CrossRef] [PubMed]
[58] Claro, I.M., Ramundo, M.S., et al. (2021) Rapid Viral Metagenomics Using SMART-9N Amplification and Nanopore Sequencing. Wellcome Open Research, 6, 241.
[59] Kafetzopoulou, L.E., Pullan, S.T., Lemey, P., Suchard, M.A., Ehichioya, D.U., Pahlmann, M., et al. (2019) Metagenomic Sequencing at the Epicenter of the Nigeria 2018 Lassa Fever Outbreak. Science, 363, 74-77. [Google Scholar] [CrossRef] [PubMed]
[60] Dutilh, B.E., Reyes, A., Hall, R.J. and Whiteson, K.L. (2017) Editorial: Virus Discovery by Metagenomics: The (Im)possibilities. Frontiers in Microbiology, 8, Article 1710. [Google Scholar] [CrossRef] [PubMed]
[61] Zeeb, M., Frischknecht, P., Balakrishna, S., Jörimann, L., Tschumi, J., Zsichla, L., et al. (2025) Addressing Data Management and Analysis Challenges in Viral Genomics: The Swiss HIV Cohort Study Viral Next Generation Sequencing Database. PLOS Digital Health, 4, e0000825. [Google Scholar] [CrossRef] [PubMed]
[62] Voigt, B., Fischer, O., Krumnow, C., Herta, C. and Dabrowski, P.W. (2021) NGS Read Classification Using AI. PLOS ONE, 16, e0261548. [Google Scholar] [CrossRef] [PubMed]
[63] Geldenhuys, M., Mortlock, M., Weyer, J., Bezuidt, O., Seamark, E.C.J., Kearney, T., et al. (2018) A Metagenomic Viral Discovery Approach Identifies Potential Zoonotic and Novel Mammalian Viruses in Neoromicia Bats within South Africa. PLOS ONE, 13, e0194527. [Google Scholar] [CrossRef] [PubMed]