scholarly journals Case Report: Next Generation Sequencing in Clinical Practice–A Real Tool for Ending the Protracted Diagnostic Odyssey

2022 ◽  
Vol 8 ◽  
Author(s):  
Alena S. Limonova ◽  
Alexandra I. Ershova ◽  
Alexey N. Meshkov ◽  
Anna V. Kiseleva ◽  
Mikhail G. Divashuk ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Correct Diagnosis ◽  
Clinical Manifestations ◽  
Disease Diagnosis ◽  
Next Generation ◽  
Lipid Clinic ◽  
Cholesterol Levels ◽  
Premature Cardiovascular Disease ◽  
Great Heterogeneity ◽  
Generation Sequencing

We reported a case of sitosterolemia, which is a rare genetic disease, characterized by increased plant sterol absorption and great heterogeneity of clinical manifestations. Our patient was initially referred to the lipid clinic due to high cholesterol levels and premature cardiovascular disease. Diagnosis of familial hypercholesterolemia was established in accordance with the Dutch Lipid Clinic Network criteria. Next-generation sequencing was later performed, which revealed a nonsense mutation in the ABCG8 gene, which led to the diagnosis of sitosterolemia. The aim of our report is to demonstrate, how genetic testing helped to make the correct diagnosis and to explain many of the patient's health problems, which etiology remained unclear for many years.

Balamuthia mandrillaris-Related Primary Amoebic Encephalitis in China Diagnosed by Next Generation Sequencing and a Review of the Literature

2019 ◽  
Author(s):  
Yinan Yang ◽  
Xiaobin Hu ◽  
Li Min ◽  
Xiangyu Dong ◽  
Yuanlin Guan
Keyword(s):  
Next Generation Sequencing ◽  
Inflammatory Diseases ◽  
Clinical Manifestations ◽  
Infectious Agent ◽  
Disease Diagnosis ◽  
Rapid Identification ◽  
Next Generation ◽  
Balamuthia Mandrillaris ◽  
Granulomatous Amoebic Encephalitis ◽  
Generation Sequencing

Abstract Background Encephalitis is caused by infection, immune mediated diseases, or primary inflammatory diseases. Of all the causative infectious pathogens, 90% are viruses or bacteria. Granulomatous amoebic encephalitis (GAE), caused by Balamuthia mandrillaris, is a rare but life-threatening disease. Diagnosis and therapy are frequently delayed due to the lack of specific clinical manifestations. Method A healthy 2 year old Chinese male patient initially presented with a nearly 2 month history of irregular fever. We present this case of granulomatous amoebic encephalitis caused by B. mandrillaris. Next generation sequencing of the patient’s cerebrospinal fluid (CSF) was performed to identify an infectious agent. Result The results of next generation sequencing of the CSF showed that most of the mapped reads belonged to Balamuthia mandrillaris. Conclusion Next generation sequencing (NGS) is an unbiased and rapid diagnostic tool. The NGS method can be used for the rapid identification of causative pathogens. The NGS method should be widely applied in clinical practice and help clinicians provide direction for the diagnosis of diseases, especially for rare and difficult cases.

scholarly journals Detection of Listeria monocytogenes in a patient with meningoencephalitis using next-generation sequencing: a case report

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zi-Wei Lan ◽  
Min-Jia Xiao ◽  
Yuan-lin Guan ◽  
Ya-Jing Zhan ◽  
Xiang-Qi Tang
Keyword(s):  
Listeria Monocytogenes ◽  
Next Generation Sequencing ◽  
Mammalian Cells ◽  
Clinical Manifestations ◽  
Bacterial Pathogen ◽  
Next Generation ◽  
Accurate Treatment ◽  
The Central Nervous System ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Background Listeria monocytogenes (L. monocytogenes) is a facultative intracellular bacterial pathogen which can invade different mammalian cells and reach to the central nervous system (CNS), leading to meningoencephalitis and brain abscesses. In the diagnosis of L. monocytogenes meningoencephalitis (LMM), the traditional test often reports negative owing to the antibiotic treatment or a low number of bacteria in the cerebrospinal fluid. To date, timely diagnosis and accurate treatment remains a challenge for patients with listeria infections. Case presentation We present the case of a 66-year-old woman whose clinical manifestations were suspected as tuberculous meningoencephalitis, but the case was finally properly diagnosed as LMM by next-generation sequencing (NGS). The patient was successfully treated using a combined antibacterial therapy, comprising ampicillin and trimethoprim-sulfamethoxazole. Conclusion To improve the sensitivity of LMM diagnosis, we used NGS for the detection of L. monocytogenes. Hence, the clinical utility of this approach can be very helpful since it provides quickly and trust results.

scholarly journals Case Report: Metagenomic Next-Generation Sequencing in Diagnosis of Talaromycosis of an Immunocompetent Patient

2021 ◽  
Vol 8 ◽  
Author(s):  
Jiejun Shi ◽  
Naibin Yang ◽  
Guoqing Qian
Keyword(s):  
Next Generation Sequencing ◽  
Pathogenic Bacteria ◽  
Clinical Decision Making ◽  
Fungal Infections ◽  
Clinical Manifestations ◽  
Whole Body ◽  
Recurrent Fever ◽  
Next Generation ◽  
Generation Sequencing ◽  
Immunocompetent Patients

Background: Talaromycosis is a serious fungal infection which is rare in immunocompetent people. Since its clinical manifestations lack specificity, it is easy to escape diagnosis or be misdiagnosed leading to high mortality and poor prognosis. It is necessary to be alert to the disease when broad-spectrum antibiotics do not work well in immunocompetent patients.Case Presentation: A 79-year-old man was admitted to our Infectious Diseases Department for recurrent fever and cough. Before admission he has been treated with piperacillin-tazobactam, moxifloxacin followed by antituberculous agents in other hospitals while his symptoms were not thoroughly eased. During the first hospitalization in another hospital, he has been ordered a series of examination including radionuclide whole body bone imaging, transbronchial needle aspiration for subcarinal nodes. However, the results were negative showing no neoplasm. After being admitted to our hospital, he underwent various routine examinations. The initial diagnosis was bacterial pneumonia, and he was given meropenem injection and tigecycline injection successively, but there were no improvement of symptoms and inflammatory indicators. In the end, the main pathogen Talaromyces marneffei was confirmed using Metagenomic Next-Generation Sequencing (mNGS), and his clinical symptoms gradually relieved after targeted antifungal treatment using voriconazole.Conclusion: When empirical anti-infective treatment is ineffective, it is necessary to consider the possibility of opportunistic fungal infections on immunocompetent patients. mNGS, as a new generation of pathogenic testing methods, can often detect pathogenic bacteria faster than traditional methods, providing important help for clinical decision-making.

scholarly journals Disseminated Strongyloides Stercoralis Hyperinfection in An Immunocompetent Patient First Diagnosed by Metagenomic Next-Generation Sequencing in Cerebrospinal Fluid: A Case Report

2021 ◽  
Author(s):  
Junyan Qu ◽  
Zhiyong Zong
Keyword(s):  
Cerebrospinal Fluid ◽  
Abdominal Pain ◽  
Next Generation Sequencing ◽  
Clinical Manifestations ◽  
Good Health ◽  
Strongyloides Stercoralis ◽  
Next Generation ◽  
Diagnostic Dilemma ◽  
Disseminated Strongyloidiasis ◽  
Generation Sequencing

Abstract Background Disseminated Strongyloides stercoralis hyperinfection is rarely described in immunocompetent individuals and can lead to fatal outcomes if not recognized and diagnosed early. Non-specific clinical manifestations, such as pneumonia and gastroenteritis, pose a diagnostic dilemma. Case presentation: We report a case of a 67-year-old Chinese male who presented with two months of abdominal pain, fever, headache, vomiting, constipation, and slight cough with sputum. He had been in good health and had no history of glucocorticoid use. He was diagnosed with enterococcal meningitis and intestinal obstruction at a local hospital and improved after treatment with vancomycin, but symptoms of headache and abdominal pain soon recurred. The metagenomic next-generation sequencing (mNGS) of the cerebrospinal fluid using Illumina X10 sequencer revealed 7 sequence reads matching Strongyloides stercoralis. Disseminated strongyloidiasis was suspected. Next, microscopic examination of gastric fluid revealed Larvae of S. stercoralis. DNA extracted of larvae, the presence of both S. stercoralis ribosomal DNA gene and mitochondrial cytochrome c oxidase subunit 1 gene was identified. Disseminated strongyloidiasis was diagnosed. Albendazole (400 mg, twice daily) was used and the patient recovered gradually. Conclusions S. stercoralis hyperinfection can occur in immunocompetent individuals, imposing challenges for diagnosis. mNGS may be a useful tool for detecting rare infectious disease. The case would help clinicians to raise awareness of strongyloidiasis in non-endemic areas and reduce fatality.

scholarly journals Metagenomic Next Generation Sequencing in the Detection of Pathogens in Cerebrospinal Fluid of Patients After Alternative Donor Transplantation: A Feasibility Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Binglei Zhang ◽  
Jian Zhou ◽  
Ruirui Gui ◽  
Zhen Li ◽  
Yingling Zu ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Next Generation Sequencing ◽  
Viral Infections ◽  
Fungal Infections ◽  
Clinical Manifestations ◽  
Next Generation ◽  
Hematopoietic Stem ◽  
Cns Infections ◽  
Alternative Donor ◽  
Generation Sequencing

Central nervous system (CNS) complications can occur in 9%–15% of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical manifestations of the CNS complications are non-specific, with most of them being disturbances of consciousness, convulsions, headaches, fever, and epilepsy, making it difficult to infer the cause of the complications based on clinical manifestations. We retrospectively analyzed the sensitivity and feasibility of metagenomic next generation sequencing (mNGS) in the diagnosis of CNS infections after allo-HSCT. Lumbar punctures were performed on 20 patients with CNS symptoms after receiving alternative donor HSCT(AD-HSCT) at the Affiliated Cancer Hospital of Zhengzhou University from February 2019 to December 2020, and their cerebrospinal fluid (CSF) was collected. The mNGS technique was used to detect pathogens in the CSF. Routine CSF testing, biochemical analyses, G experiments, GM experiments, ink staining, acid-fast staining, and bacterial cultures were carried out, and quantitative PCR (qPCR) tests were used to detect cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK polyomavirus (BKPyV), and human alphaherpesvirus (HHV). A total of 29 tests were performed with 21 of them being positive. Of the five negative patients, three were diagnosed with a posterior reversible encephalopathy syndrome, one as having transplantation-associated thrombotic microangiopathy, and one with transient seizure caused by hypertension. Fifteen patients tested positive, of which four had single infections and eleven had mixed infections. Five cases of fungal infections, six cases of bacterial infections, and 13 cases of viral infections were detected. Among the 13 cases of viral infections, ten cases were CMV(HHV-5); three were BKPyV; two were Torque teno virus (TTV); Two were HHV-1,two were EBV(HHV4), and one each of HpyV5 and HHV-6B. Thirteen patients tested positive for virus while the qPCR detection method of 6 identical specimens were below the minimum detection limit(<1×103 U/ml). The mNGS technique is highly sensitive, and it can be used to diagnose CNS infections after allo-HSCT.

Efficient application of next-generation sequencing for the diagnosis of rare genetic syndromes

2014 ◽  
Vol 67 (12) ◽  
pp. 1099-1103 ◽  
Author(s):  
Irene Madrigal ◽  
Maria Isabel Alvarez-Mora ◽  
Olof Karlberg ◽  
Laia Rodríguez-Revenga ◽  
Dei M Elurbe ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Next Generation Sequencing ◽  
Genetic Diseases ◽  
Genetic Defect ◽  
Disease Diagnosis ◽  
Underlying Disease ◽  
Next Generation ◽  
Genetic Syndromes ◽  
Biomedical Diagnosis ◽  
Generation Sequencing

AimsThe causes of intellectual disability, which affects 1%–3% of the general population, are highly heterogeneous and the genetic defect remains unknown in around 40% of patients. The application of next-generation sequencing is changing the nature of biomedical diagnosis. This technology has quickly become the method of choice for searching for pathogenic mutations in rare uncharacterised genetic diseases.MethodsWhole-exome sequencing was applied to a series of families affected with intellectual disability in order to identify variants underlying disease phenotypes.ResultsWe present data of three families in which we identified the disease-causing mutations and which benefited from receiving a clinical diagnosis: Cornelia de Lange, Cohen syndrome and Dent-2 disease. The genetic heterogeneity and the variability in clinical presentation of these disorders could explain why these patients are difficult to diagnose.ConclusionsThe accessibility to next-generation sequencing allows clinicians to save much time and cost in identifying the aetiology of rare diseases. The presented cases are excellent examples that demonstrate the efficacy of next-generation sequencing in rare disease diagnosis.

scholarly journals Inherited Paediatric Motor Neuron Disorders: Beyond Spinal Muscular Atrophy

2017 ◽  
Vol 2017 ◽  
pp. 1-22 ◽  
Author(s):  
Hooi Ling Teoh ◽  
Kate Carey ◽  
Hugo Sampaio ◽  
David Mowat ◽  
Tony Roscioli ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Protein Quality ◽  
Neurodegenerative Disorder ◽  
Muscular Atrophy ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Next Generation ◽  
Generation Sequencing

Paediatric motor neuron diseases encompass a group of neurodegenerative diseases characterised by the onset of muscle weakness and atrophy before the age of 18 years, attributable to motor neuron loss across various neuronal networks in the brain and spinal cord. While the genetic underpinnings are diverse, advances in next generation sequencing have transformed diagnostic paradigms. This has reinforced the clinical phenotyping and molecular genetic expertise required to navigate the complexities of such diagnoses. In turn, improved genetic technology and subsequent gene identification have enabled further insights into the mechanisms of motor neuron degeneration and how these diseases form part of a neurodegenerative disorder spectrum. Common pathophysiologies include abnormalities in axonal architecture and function, RNA processing, and protein quality control. This review incorporates an overview of the clinical manifestations, genetics, and pathophysiology of inherited paediatric motor neuron disorders beyond classic SMN1-related spinal muscular atrophy and describes recent advances in next generation sequencing and its clinical application. Specific disease-modifying treatment is becoming a clinical reality in some disorders of the motor neuron highlighting the importance of a timely and specific diagnosis.

scholarly journals A case of chlamydia psittaci caused severe pneumonia and meningitis diagnosed by metagenome next-generation sequencing and clinical analysis: a case report and literature review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yunfeng Shi ◽  
Junxian Chen ◽  
Xiaohan Shi ◽  
Jiajia Hu ◽  
Hongtao Li ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Fatal Case ◽  
Invasive Mechanical Ventilation ◽  
Clinical Manifestations ◽  
Severe Pneumonia ◽  
Chlamydia Psittaci ◽  
Gene Probe ◽  
Atypical Pneumonia ◽  
Next Generation ◽  
Generation Sequencing

Abstract Background Psittacosis, which is also known as parrot fever, is Chlamydia psittaci (C. psittaci) caused infectious disease. The clinical manifestations vary from asymptomatic infection to severe atypical pneumonia or even fatal meningitis. Early recognition of psittacosis is difficult because of its nonspecific clinical manifestations. Culture and gene probe techniques for C. psittaci are not available for routine clinical use, which makes the diagnosis difficult too. Although psittacosis has increasingly been recognized and reported in recent years, cure of severe pneumonia complicated with meningitis, with etiologic diagnosis aided by the use of metagenomic next-generation sequencing (mNGS), is still uncommon. So, it is necessary to report and review such potentially fatal case. Case presentation This report describes a 54-year-old woman with C. psittaci caused severe atypical pneumonia and meningitis. She presented with symptoms of fever, dry cough and dyspnea, accompanied by prominent headache. Her condition deteriorated rapidly to respiratory failure and lethargy under the treatment of empirical antibacterial agents, and was treated with invasive mechanical ventilation soon. She denied contact with birds, poultry or horses, but unbiased mNGS of both the bronchoalveolar lavage fluid (BALF) and the cerebrospinal fluid (CSF) identified sequence reads corresponding to C. psittaci infection, and there was no sequence read corresponding to other probable pathogens. Combined use of targeted antimicrobial agents of tetracyclines, macrolides and fluoroquinolones was carried out, and the patient’s condition improved and she was discharged home 28 days later. Her status returned close to premorbid condition on day 60 of follow-up. Conclusions When clinicians come across a patient with atypical pneumonia accompanied by symptoms of meningitis, psittacosis should be taken into consideration. mNGS is a promising detection method in such condition and is recommended.

scholarly journals Next-generation sequencing combined with serological tests based pathogen analysis for a neurocysticercosis patient with a 20-year history:a case report

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bin Chen ◽  
Zheng Chen ◽  
Yi-shu Yang ◽  
Gui-lan Cai ◽  
Xiao-jiao Xu ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Taenia Solium ◽  
Clinical Manifestations ◽  
Next Generation ◽  
Serum Samples ◽  
Igg Antibody ◽  
Serological Tests ◽  
Diagnostic Efficacy ◽  
Variable Sensitivity ◽  
Generation Sequencing

Abstract Background Neurocysticercosis (NCC) is the most common helminthic infection of the central nervous system (CNS) caused by the larval stage of Taenia solium. Accurate and early diagnosis of NCC remains challenging due to its heterogeneous clinical manifestations, neuroimaging deficits, variable sensitivity, and specificity of serological tests. Next-generation sequencing (NGS)-based pathogen analysis in patient’s cerebrospinal fluid (CSF) with NCC infection has recently been reported indicating its diagnostic efficacy. In this case study, we report the diagnosis of a NCC patient with a symptomatic history of over 20 years using NGS analysis and further confirmation of the pathology by immunological tests. Case presentation This study reports the clinical imaging and immunological features of a patient with a recurrent headache for more than 20 years, which worsened gradually with the symptom of fever for more than 7 years and paroxysmal amaurosis for more than 1 year. By utilizing NGS technique, the pathogen was detected in patient’s CSF, and the presence of Taenia solium-DNA was confirmed by a positive immunological reaction to cysticercus IgG antibody in CSF and serum samples. The symptoms of the patient were alleviated, and the CSF condition was improved substantially after the anti-helminthic treatment. Conclusions This study suggests that combining CSF NGS with cysticercus IgG testing may be a highly promising approach for diagnosing the challenging cases of NCC. Further studies are needed to evaluate the parasitic DNA load in patients’ CSF for the diagnosis of disease severity, stage, and monitoring of therapeutic responses.

scholarly journals Application of metagenomic next-generation sequencing in the diagnosis of severe pneumonia caused by Chlamydia psittaci

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Huan-huan Wu ◽  
Lan-fang Feng ◽  
Shuang-yan Fang
Keyword(s):  
Mechanical Ventilation ◽  
Next Generation Sequencing ◽  
Invasive Mechanical Ventilation ◽  
False Negative ◽  
Clinical Manifestations ◽  
Severe Pneumonia ◽  
Chlamydia Psittaci ◽  
Diagnostic Tools ◽  
Next Generation ◽  
Generation Sequencing

Abstract Purpose Psittacosis is a zoonotic infectious disease caused by the transmission of the bacterium Chlamydia psittaci (C. psittaci) from birds to humans. Infections in humans mainly present as community-acquired pneumonia (CAP). However, most cases are treated without diagnostic testing, and the importance of Chlamydia psittaci infection as a cause of CAP is therefore unclear. Diagnostic tools, including culture, serologic test, and PCR-based methods, are available but prone to false negative results. Metagenomic next-generation sequencing (mNGS) has been increasingly used in the diagnosis of infectious diseases, particularly when conventional diagnostic approaches have limitation. Detection of nucleic acid sequence of C. psittaci in respiratory tract samples by metagenomic next-generation sequencing (mNGS) is effective for early diagnosis of severe C. psittaci pneumonia. Timely treatment based on tetracycline can reduce unnecessary use of antibiotics and improve prognosis of patients with severe C. psittaci pneumonia. Methods Clinical data of thirteen patients with severe C. psittaci pneumonia diagnosed by mNGS were collected. Clinical manifestations, treatment and prognosis of patients were summarized. Results The typical symptoms of pneumonia caused by C. psittaci include fever, headache, myalgia, cough, and dyspnea. In the current study, all patients met the criteria for severe C. psittaci pneumonia and received mechanical ventilation, including noninvasive mechanical ventilation (five/thirteen) and invasive mechanical ventilation (eight/thirteen). The findings showed that patients with C. psittaci pneumonia presented with normal or slightly increased leucocytes and procalcitonin, and high C-reactive protein levels. Computed tomography manifestations included consolidation of lung parenchyma, with air bronchogram and pleural effusion in some patients. mNGS analysis results were obtained within 48–72 h. Eleven patients fully recovered after targeted treatment, however, two patients died from secondary multidrug-resistant Pseudomonas aeruginosa infection. Conclusions The findings of the current study show that mNGS is effective in diagnosis of C. psittaci pneumonia, and has significant diagnosis value in patients with severe infection. Patients responds well to the timely use of appropriate antibiotics.

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