Metagenomic next-generation sequencing

宏基因组下一代测序
  • 文章类型: Case Reports
    BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) that is responsible for deformities and irreversible peripheral nerve damage and has a broad spectrum of clinical and serological manifestations. Leprosy primarily affects the peripheral nerves and rarely presents with central nervous system involvement. Diagnosing leprosy can still be difficult in some cases, especially when the infection involves uncommon clinical manifestations and extracutaneous sites. Delayed diagnosis and treatment of leprosy may lead to irreversible damage and death.
    METHODS: We report a case of a 30-year-old female presenting with \"repeated high fever with symptoms of headache for 14 days\". On the day of admission, physical signs of lost eyebrows and scattered red induration patches all over her body were observed. The patient\'s diagnosis was based on the clinical characteristics using a combination of metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and slit-skin smear. After confirming Listeria meningitis and multibacillary leprosy with erythema nodosum leprosum (ENL), a type 2 reaction, she was treated with ampicillin sodium, dapsone, rifampicin, clofazimine, methylprednisolone, and thalidomide. At the 1-year follow-up, the frequency and severity of headaches have significantly decreased and a good clinical response with improved skin lesions was found.
    CONCLUSIONS: This case highlights the importance of considering leprosy, which is a rare and underrecognized disease, in the differential diagnosis of skin rashes with rheumatic manifestations, even in areas where the disease is not endemic, and physicians should be alerted about the possibility of central nervous system infections. In addition, mNGS can be used as a complementary diagnostic tool to traditional diagnostic methods to enhance the diagnostic accuracy of leprosy.
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  • 文章类型: Case Reports
    卡氏棘阿米巴感染是一种罕见的疾病,主要发生在免疫功能低下的患者中,死亡率极高。目前,这种情况没有标准的治疗方法,成功的治疗报告很少。
    我们介绍了一例63岁女性艾滋病患者感染卡斯特阿米巴的病例,他因发烧症状入院,皮肤溃疡,皮下结节,进食时鼻子的食物反流。在最初的经验治疗失败后,对皮下结节进行了活检,宏基因组下一代测序(mNGS)技术用于检测活检标本和血液样本中的病原微生物。结果显示卡氏棘阿米巴感染。此外,活检标本的组织病理学检查和溃疡表面分泌物的细胞学检查也证实了这种致病性感染。在调整治疗方案以抗阿米巴治疗的组合后,患者的症状在出院时显著改善。
    出现不明原因发热和皮肤或鼻窦病变的免疫功能低下患者应进行卡氏棘阿米巴感染评估。这种生物感染需要多种药物联合治疗,标准治疗方案仍需进一步研究。宏基因组下一代测序是早期诊断未知病原体感染的有价值的工具。
    UNASSIGNED: Acanthamoeba castellanii infection is a rare condition primarily occurring in immunocompromised patients with extremely high mortality. Currently, there is no standard treatment for this condition, and successful treatment reports are scarce.
    UNASSIGNED: We present a case of Acanthamoeba castellanii infection in a 63-year-old female patient with AIDS, who was admitted to our hospital with symptoms of fever, skin ulcers, subcutaneous nodules, and food regurgitation from the nose while eating. After initial empirical treatment failed, a biopsy of the subcutaneous nodule was performed, and metagenomic next-generation sequencing (mNGS) technology was used to detect pathogenic microorganisms in both the biopsy specimen and blood samples. The results revealed Acanthamoeba castellanii infection. Additionally, histopathological examination of the biopsy specimen and cytological examination of the secretions from the ulcer surface also confirmed this pathogenic infection. The patient\'s symptoms significantly improved upon discharge after adjusting the treatment regimen to a combination of anti-amebic therapy.
    UNASSIGNED: Immunocompromised patients presenting with unexplained fever and skin or sinus lesions should be evaluated for Acanthamoeba castellanii infection. Multi-drug combination therapy is required for this organism infection, and a standard treatment protocol still needs further research. Metagenomic next-generation sequencing is a valuable tool for early diagnosis of unknown pathogen infections.
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  • 文章类型: Journal Article
    背景:人类嗜色杆菌分布广泛,主要感染免疫功能受损的患者。历史上,O.anthropi被认为具有低毒性和致病性;然而,最近的研究表明,它实际上可能导致严重的化脓性感染。在这个案例研究中,我们检查了一例角膜移植后的O.anthropi感染,探讨此类术后感染的发生和结果。
    方法:回顾性分析涉及检查的病例,基因检测用于诊断,以及后续治疗。在接受部分穿透性角膜移植术并伴有真菌性角膜溃疡穿孔的患者中,术后观察到前房渗出和化脓。尽管有抗真菌治疗,前房液和化脓性物质的遗传测试证实了O.人品感染。发现使用特异性靶向O.anthropi的抗微生物治疗可有效治疗感染。
    结论:应监测角膜移植后的炎症反应是否存在其他感染。基因检测对临床诊断和治疗具有重要意义。
    BACKGROUND: Ochrobactrum anthropi is widely distributed and primarily infects patients with compromised immune functions . Historically, O. anthropi has been considered to possess low toxicity and pathogenicity; however, recent studies suggest that it may in fact cause severe purulent infections. In this case study, we examine a case of O. anthropi infection following corneal transplantation, exploring the occurrence and outcomes of such post-operative infections.
    METHODS: A retrospective analysis of cases involved examinations, genetic testing for diagnosis, and subsequent treatment. In patients undergoing partial penetrating keratoplasty with a fungal corneal ulcer perforation, anterior chamber exudation and purulence were observed post-surgery. Despite antifungal treatment, genetic testing of the anterior chamber fluid and purulent material confirmed O. anthropi infection. The use of antimicrobial treatment specifically targeting O. anthropi was found to be effective in treating the infection.
    CONCLUSIONS: Inflammatory reactions following corneal transplantation should be should be monitored for the presence of other infections. Genetic testing has significant implications for clinical diagnosis and treatment.
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  • 文章类型: Case Reports
    背景:血小板减少综合征(SFTS)是由SFTS病毒(SFTSV)引起的蜱传疾病,有可能成为大流行,目前是主要的公共卫生问题。
    方法:我们介绍了一个来自重庆市区的74岁女性的案例,白细胞减少症,血小板减少症,器官功能,炎症,血液凝固,和免疫异常。通过分子检测和宏基因组下一代测序(mNGS)分析证实了SFTSV感染,由于患者的蜱叮咬史,表明SFTS的诊断。患者接受对症和支持治疗,包括抗生素,抗病毒治疗,和抗真菌治疗,终于在第18天出院了.
    结论:这项研究强调了提高意识的必要性,早期诊断,并迅速治疗蜱传SFTS。它还提供了一个全面的了解疾病的特点,发病机制,检测方法,和可用的治疗方法。
    BACKGROUND: Severe Fever with Thrombocytopenia Syndrome (SFTS) is a tick-borne disease caused by the SFTS virus (SFTSV) which has the potential to become a pandemic and is currently a major public health concern.
    METHODS: We present the case of a 74-year-old female from an urban area of Chongqing, with leukocytopenia, thrombocytopenia, organ function, inflammatory, blood coagulation, and immune abnormalities. SFTSV infection was confirmed through molecular detection and metagenomic next-generation sequencing (mNGS) analysis, indicating a diagnosis of SFTS due to the patient\'s history of tick bites. The patient received symptomatic and supportive therapy, including antibiotics, antiviral treatment, and antifungal therapy, and finally discharged from the hospital on day 18.
    CONCLUSIONS: This study highlights the need for increased awareness, early diagnosis, and prompt treatment for tick-borne SFTS. It also provides a comprehensive understanding of the disease\'s characteristics, pathogenesis, detection methods, and available treatments.
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  • 文章类型: Journal Article
    背景:猫抓病(CSD)是由巴尔通体感染引起的。在CSD的非典型病例中,病原体测定是具有挑战性的。我们报告了一例巴尔通体神经性视网膜炎,既没有明显的划痕史,也没有典型的一般症状。使用宏基因组下一代测序(mNGS)进行诊断,高通量测序技术。
    方法:一名女性患者向眼科医生就诊,主诉右眼视力模糊。虽然有养猫的历史,她没有明确的抓痕史或典型的一般症状,除了不明原因的发烧自发解决。右眼的最佳矫正视力(BCVA)是计数手指。眼底检查显示视盘水肿,黄斑渗出和下渗出性视网膜脱离。实验室检查结果显示血清C反应蛋白和红细胞沉降率升高。弓形虫病眼部受累,梅毒和肺结核被排除。为了确定该疾病的可能致病病原体,进行房水样品的mNGS,并鉴定了521个Henselae的读数。血清学测试结果进一步显示1:64的阳性免疫球蛋白G(IgG)滴度。以接触历史为例,临床表现,考虑到mNGS和血清学结果,诊断为巴尔通体神经性视网膜炎(眼CSD)。经过适当的治疗,在最后一次随访中,右眼的BCVA改善为20/25。眼底检查显示视盘和黄斑正常,分泌物减少了.
    结论:mNGS,一种快速而公正的方法,可用于检测眼内液样品中的B.henselae(如果存在)。;然而,结果应与临床症状和其他辅助检查结果一起解释。
    BACKGROUND: Cat-scratch disease (CSD) is caused by Bartonella henselae infection. In atypical cases of CSD, pathogen determination is challenging. We report a case of Bartonella neuroretinitis with neither a clear history of scratches nor typical general symptoms. The diagnosis was made using metagenomic next-generation sequencing (mNGS), a high-throughput sequencing technology.
    METHODS: A female patient presented to the ophthalmologist with complaint of blurred vision in her right eye. Although with history of raising a cat, she reported no clear history of scratches or typical general symptoms, except a fever of unknown origin which resolved spontaneously. The best corrected visual acuity (BCVA) of the right eye was count fingers. Fundus examination showed optic disc oedema, macular exudates and inferior exudative retinal detachment. Laboratory examination results showed increased value of serum C-reactive protein and erythrocyte sedimentation rate. Ocular involvement of toxoplasmosis, syphilis and tuberculosis were excluded. To identify the possible causative pathogen of the disease, mNGS of aqueous humour sample was performed and 521 reads of B. henselae were identified. Serological test results further showed a positive immunoglobulin G (IgG) titre of 1:64. Taking the contact history, clinical manifestations, mNGS and serological results into consideration, the diagnosis of Bartonella neuroretinitis (ocular CSD) was made. After appropriate treatment, the BCVA of the right eye improved to 20/25 in the last follow-up. Fundus examination showed a normal optic disc and macula, and the exudates had reduced.
    CONCLUSIONS: mNGS, a fast and unbiased method, can be used to detect B. henselae (if present) in intraocular fluid samples.; however, the results should be interpreted together with the clinical symptoms and other auxiliary test results.
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  • 文章类型: Review
    背景:Scedosporiumapiospermum(S.apiospermum)是一种罕见的真菌病原体,可引起播散性感染。它很少影响有免疫能力的个体,并且预后不良。
    方法:一名37岁女性肺部多发病变,大脑,和眼睛,在一场车祸中险些溺水后不久。主要症状是胸闷,四肢无力,头痛,左眼视力差.通过颅内脓肿引流液的宏基因组下一代测序(mNGS)证实了枯草菌感染,尽管最初考虑颅内转移。伏立康唑全身治疗后,她的症状明显改善;然而,由于延误诊断,她的左眼失去了视力。
    结论:虽然吸精菌感染很少见,即使在有免疫能力的患者中也应考虑。及时的诊断和治疗至关重要。伏立康唑可能是一种有效的治疗选择。
    BACKGROUND: Scedosporium apiospermum (S. apiospermum) is a rare fungal pathogen that causes disseminated infections. It rarely affects immunocompetent individuals and has a poor prognosis.
    METHODS: A 37-year-old woman presented with multiple lesions in the lungs, brain, and eyes, shortly after near drowning in a car accident. The primary symptoms were chest tightness, limb weakness, headache, and poor vision in the left eye. S. apiospermum infection was confirmed by metagenomic next-generation sequencing (mNGS) of intracranial abscess drainage fluid, although intracranial metastases were initially considered. After systemic treatment with voriconazole, her symptoms improved significantly; however, she lost vision in her left eye due to delayed diagnosis.
    CONCLUSIONS: While S. apiospermum infection is rare, it should be considered even in immunocompetent patients. Prompt diagnosis and treatment are essential. Voriconazole may be an effective treatment option.
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  • 文章类型: Case Reports
    非结核分枝杆菌相关颅内感染是一种罕见疾病,主要发生在HIV感染患者中。该病预后不良。作者报告了一例非AIDS患者的非结核性分枝杆菌脑膜脑炎,但2型糖尿病控制不佳的长期病史。一位55岁的老人,右撇子,男性患者有8天的发热史,伴有脑膜刺激症状的严重头痛发作。MRI显示视觉通路的高强度/对比度增强,基底神经节鞍区和软脑膜。在使用宏基因组下一代测序(mNGS)之前,没有达到病因诊断,显示分枝杆菌的存在。该患者通过积极的抗分枝杆菌疗法治愈。作者通过复习相关文献,讨论非结核分枝杆菌相关性颅内感染的临床表现和药物治疗。由于鸟分枝杆菌引起的脑膜脑炎具有很高的死亡率,因此需要早期诊断和适当的治疗干预措施。出于这个原因,使用mNGS有助于避免治疗延迟。
    Nontuberculous mycobacteria associated intracranial infection is a rare disease that mainly occurs in HIV-infected patients. The disease has a poor prognosis. The authors report a case of non-tuberculous mycobacterial meningoencephalitis in a non-AIDS patient, but long history of poorly controlled type 2 diabetes mellitus. A 55-year-old, right-handed, male patient presented with an 8-day history of fever, episodes of severe headache with signs of meningeal irritation. MRI showed hyperintensities/contrast enhancement in the visual pathways, basal ganglia sellar region and leptomeninges. No etiological diagnosis was reached until metagenomic next-generation sequencing (mNGS) was used, showing the presence of Mycobacterium avium. The patient was cured with aggressive antimycobacterial therapy. The authors discuss the clinical manifestations and drug therapy of nontuberculous mycobacteria-related intracranial infections by reviewing relevant literature. As meningoencephalitis by Mycobacterium avium has a high mortality an early diagnosis and appropriate therapeutic interventions are warranted. For this reason, the use of mNGS can be helpful to avoid therapeutic delay.
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  • 文章类型: Review
    背景:诺卡氏菌是引起人类感染的最常见诺卡氏菌之一。它是一种机会性病原体,经常感染免疫系统受损的人。它可以通过呼吸道或皮肤伤口侵入人体,引起局部感染,并通过血行播散影响其他器官。然而,法氏杆菌引起的菌血症并不常见。在这项研究中,我们报道了中国1例土豆素引起的菌血症。
    方法:北京协和医院收治一名80岁女性,因反复发热,右腹痛了一个半月,和右肾上腺的占领。使用血液培养和血浆宏基因组学下一代测序(mNGS)鉴定了N.Farcinica为致病病原体。临床考虑因素包括由诺卡氏菌感染引起的菌血症和肾上腺脓肿。因为病人对磺胺过敏,对亚胺培南/西司他丁和利奈唑胺进行经验性给药。不幸的是,患者最终在开始抗感染治疗后不到一个月死亡.
    结论:N.Farcinica菌血症很少见,其临床表现没有特异性。它的诊断取决于病因检查,这可以使用Sanger测序和mNGS等技术来证实。在这份报告中,我们回顾了过去十年报告的诺卡氏菌血流感染病例,希望能提高临床医师对诺卡氏菌血流感染的认识,并对其早期诊断和及时治疗有所帮助。
    BACKGROUND: Nocardia farcinica is one of the most common Nocardia species causing human infections. It is an opportunistic pathogen that often infects people with compromised immune systems. It could invade human body through respiratory tract or skin wounds, cause local infection, and affect other organs via hematogenous dissemination. However, N. farcinica-caused bacteremia is uncommon. In this study, we report a case of bacteremia caused by N. farcinica in China.
    METHODS: An 80-year-old woman was admitted to Peking Union Medical College Hospital with recurrent fever, right abdominal pain for one and a half month, and right adrenal gland occupation. N. farcinica was identified as the causative pathogen using blood culture and plasma metagenomics next-generation sequencing (mNGS). The clinical considerations included bacteremia and adrenal gland abscess caused by Nocardia infection. As the patient was allergic to sulfanilamide, imipenem/cilastatin and linezolid were empirically administered. Unfortunately, the patient eventually died less than a month after the initiation of anti-infection treatment.
    CONCLUSIONS: N. farcinica bacteremia is rare and its clinical manifestations are not specific. Its diagnosis depends on etiological examination, which can be confirmed using techniques such as Sanger sequencing and mNGS. In this report, we have reviewed cases of Nocardia bloodstream infection reported in the past decade, hoping to improve clinicians\' understanding of Nocardia bloodstream infection and help in its early diagnosis and timely treatment.
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  • 文章类型: Case Reports
    一名接受奥拉帕尼维持治疗的52岁女性患者因低烧和胸闷入院。患者胸部CT扫描显示双肺弥漫性毛玻璃影或绒状结节影。她的炎症生物标志物几乎正常,除了C反应蛋白略有升高.此外,淋巴细胞计数明显下降。经验性治疗并没有缓解她的症状,而传统的测试结果为阴性。宏基因组下一代测序(mNGS)的结果表明存在潜在的病原体,放线菌(A.牙本质细胞),支气管肺泡灌洗液(BLAF)。一旦服用大剂量青霉素G,发烧恢复正常,胸闷消失。胸部CT复查显示肺部病变几乎吸收。我们的案例表明,mNGS是一种灵敏而准确地识别病原体的新方法,尤其是不常见和不典型的感染。
    A 52-year-old female patient receiving olaparib maintenance treatment was admitted to hospital with a low fever and chest tightness. A CT scan of the patient\'s chest showed diffuse ground glass shadow or miliary nodular shadow in the bilateral lungs. Her inflammatory biomarkers were almost normal, except the slightly elevated C-reactive protein. Moreover, lymphocytes count obviously decreased. Empirical treatment did not relieve her symptoms, while traditional testing developed negative results. The results of metagenomic next-generation sequencing (mNGS) revealed the presence of a potential pathogen, Actinomyces odontolyticus (A. odontolyticus), in bronchoalveolar lavage fluid (BLAF). Once large-dosed penicillin G was administered, the fever returned to normal and chest tightness disappeared. Reexamination of chest CT revealed that the pulmonary lesions was almost absorbed. Our case demonstrated that mNGS is a novel approach to identify pathogens sensitively and accurately, especially for uncommon and atypical infection.
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  • 文章类型: Review
    Scedosporiumapiospermum物种复合体是广泛分布的真菌,可以在各种污染环境中发现,包括土壤,污水,和腐烂的植被。那些具有强烈入侵潜力的机会病原体通常会影响免疫抑制人群。在有免疫能力的个体中报道了很少的丝孢子虫病病例,可能会被误诊,导致高死亡率。这里,我们报道了一例涉及肺部的全身感染的免疫功能正常的病例,大脑和脊柱,由S.apiospermum物种复合体(S.apiospermum和S.boydii)。该患者是一名老年男性,在接近溺水后持续发烧和系统感染。在他参观的两家三级医院,明确的诊断是极其困难的。入院后,他被误诊为结核感染,在通过宏基因组下一代测序诊断出夏枯草物种复杂感染之前。伏立康唑治疗后症状缓解。在目前的情况下,报道了与其病程相关的详细信息,并发表了有关Scedosporiumspp的研究。感染也进行了审查,更好地了解本病,减少误诊率。
    Scedosporium apiospermum species complex are widely distributed fungi that can be found in a variety of polluted environments, including soil, sewage, and decaying vegetation. Those opportunistic pathogens with strong potential of invasion commonly affect immunosuppressed populations However, few cases of scedosporiosis are reported in immunocompetent individuals, who might be misdiagnosed, leading to a high mortality rate. Here, we reported an immunocompetent case of systemtic infection involved in lung, brain and spine, caused by S. apiospermum species complex (S. apiospermum and S. boydii). The patient was an elderly male with persistent fever and systemtic infection after near-drowning. In the two tertiary hospitals he visited, definite diagnosis was extremely difficult. After being admitted to our hospital, he was misdiagnosed as tuberculosis infection, before diagnosis of S. apiospermum species complex infection by the metagenomic next-generation sequencing. His symptoms were alleviated after voriconazole treatment. In the present case, the details associated with its course were reported and published studies on Scedosporium spp. infection were also reviewed, for a better understanding of this disease and reducing the misdiagnosis rate.
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