scholarly journals Performance of Metagenomic Next-Generation Sequencing for the Diagnosis of Viral Meningoencephalitis in a Resource-Limited Setting

2020 ◽  
Vol 7 (3) ◽  
Author(s):  
Nguyen Thi Thu Hong ◽  
Nguyen To Anh ◽  
Nguyen Thi Hoang Mai ◽  
Ho Dang Trung Nghia ◽  
Le Nguyen Truc Nhu ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Infectious Diseases ◽  
Wide Spectrum ◽  
Mumps Virus ◽  
Resource Limited Setting ◽  
Next Generation ◽  
Resource Limited Settings ◽  
Resource Limited ◽  
Generation Sequencing ◽  
Limited Setting

Abstract Background Meningoencephalitis is a devastating disease worldwide. Current diagnosis fails to establish the cause in ≥50% of patients. Metagenomic next-generation sequencing (mNGS) has emerged as pan-pathogen assays for infectious diseases diagnosis, but few studies have been conducted in resource-limited settings. Methods We assessed the performance of mNGS in the cerebrospinal fluid (CSF) of 66 consecutively treated adults with meningoencephalitis in a tertiary referral hospital for infectious diseases in Vietnam, a resource-limited setting. All mNGS results were confirmed by viral-specific polymerase chain reaction (PCR). As a complementary analysis, 6 viral PCR-positive samples were analyzed using MinION-based metagenomics. Results Routine diagnosis could identify a virus in 15 (22.7%) patients, including herpes simplex virus (HSV; n = 7) and varicella zoster virus (VZV; n = 1) by PCR, and mumps virus (n = 4), dengue virus (DENV; n = 2), and Japanese encephalitis virus (JEV; n = 1) by serological diagnosis. mNGS detected HSV, VZV, and mumps virus in 5/7, 1/1, and 1/4 of the CSF positive by routine assays, respectively, but it detected DENV and JEV in none of the positive CSF. Additionally, mNGS detected enteroviruses in 7 patients of unknown cause. Metagenomic MinION-Nanopore sequencing could detect a virus in 5/6 PCR-positive CSF samples, including HSV in 1 CSF sample that was negative by mNGS, suggesting that the sensitivity of MinION is comparable with that of mNGS/PCR. Conclusions In a single assay, metagenomics could accurately detect a wide spectrum of neurotropic viruses in the CSF of meningoencephalitis patients. Further studies are needed to determine the value that real-time sequencing may contribute to the diagnosis and management of meningoencephalitis patients, especially in resource-limited settings where pathogen-specific assays are limited in number.

scholarly journals A Case of Streptococcus Suis Meningitis With Visual Impairment and Hearing Loss Diagnosed by Metagenomic Next-generation Sequencing

2021 ◽  
Author(s):  
Haina Zhao ◽  
Lanlan Chen ◽  
Lin Zhu ◽  
Tingting Qiao ◽  
Peipei Liu ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Hearing Loss ◽  
Next Generation Sequencing ◽  
Infectious Diseases ◽  
Visual Impairment ◽  
Vision Loss ◽  
Streptococcus Suis ◽  
Next Generation ◽  
The Right ◽  
Generation Sequencing

Abstract Background: Streptococcus suis is responsible for several kinds of zoonosis worldwide. It can cause meningitis, sepsis, osteoarthritis, endocarditis, endophthalmitis, and other diseases. Human infection typically occurs in occupational settings associated with pig husbandry or pork processing. At present, metagenomic next-generation sequencing (mNGS) is prominent testing method for achieving an early and rapid diagnosis of some infectious diseases. Case presentation: A 48-year-old Chinese man who denied exposure to pigs or pork was to admitted the hospital because he had experienced a fever for three days, visual impairment, and hearing loss for one day. After a series of examinations and laboratory tests, Streptococcus suis was detected in the aqueous humor culture as well as the vitreous humor and cerebrospinal fluid with mNGS. But bacteria were not detected in the blood or cerebrospinal fluid culture. The patient's condition improved, and he was discharged after 2 weeks of active treatment. However, at present, poor vision in the right eye, poor hearing in the right ear and recurrent vertigo remain.Conclusions: In a patient presenting with meningitis, vision loss, and/or hearing loss, Streptococcus suis infection should be strongly suspected regardless of the patient's occupation. mNGS has excellent diagnostic value to determine which was the etiological agent for infectious diseases.

scholarly journals Etiology of fever in Ugandan children: identification of microbial pathogens using metagenomic next-generation sequencing and IDseq, a platform for unbiased metagenomic analysis

2018 ◽  
Author(s):  
Akshaya Ramesh ◽  
Sara Nakielny ◽  
Jennifer Hsu ◽  
Mary Kyohere ◽  
Oswald Byaruhanga ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Pilot Study ◽  
Infectious Diseases ◽  
Parvovirus B19 ◽  
Human Herpesvirus ◽  
Febrile Illness ◽  
Microbial Pathogens ◽  
Next Generation ◽  
Syncytial Virus ◽  
Generation Sequencing

AbstractBackgroundFebrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. We built and employed IDseq, a cloud-based, open access, bioinformatics platform and service to identify microbes from metagenomic next-generation sequencing of tissue samples. In this pilot study, we evaluated blood, nasopharyngeal, and stool specimens from 94 children (aged 2-54 months) with febrile illness admitted to Tororo District Hospital, Uganda.ResultsThe most common pathogens identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from blood; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. Among other potential pathogens, we identified one novel orthobunyavirus, tentatively named Nyangole virus, from the blood of a child diagnosed with malaria and pneumonia, and Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis. We also identified two novel human rhinovirus C species.ConclusionsThis exploratory pilot study demonstrates the utility of mNGS and the IDseq platform for defining the molecular landscape of febrile infectious diseases in resource limited areas. These methods, supported by a robust data analysis and sharing platform, offer a new tool for the surveillance, diagnosis, and ultimately treatment and prevention of infectious diseases.

scholarly journals Precision Medicine and Precision Public Health in the Era of Pathogen Next-Generation Sequencing

2019 ◽  
Vol 221 (Supplement_3) ◽  
pp. S289-S291 ◽  
Author(s):  
Mariana Leguia ◽  
Anton Vila-Sanjurjo ◽  
Patrick S G Chain ◽  
Irina Maljkovic Berry ◽  
Richard G Jarman ◽  
...  
Keyword(s):  
Public Health ◽  
Next Generation Sequencing ◽  
Infectious Diseases ◽  
Next Generation ◽  
The Past ◽  
Infectious Disease Research ◽  
History Of ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Health Applications

Abstract This brief report serves as an introduction to a supplement of the Journal of Infectious Diseases entitled “Next-Generation Sequencing (NGS) Technologies to Advance Global Infectious Disease Research.” We briefly discuss the history of NGS technologies and describe how the techniques developed during the past 40 years have impacted our understanding of infectious diseases. Our focus is on the application of NGS in the context of pathogen genomics. Beyond obvious clinical and public health applications, we also discuss the challenges that still remain within this rapidly evolving field.

scholarly journals Clinical application of cell-free next-generation sequencing for infectious diseases at a tertiary children’s hospital

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Julianne Wilke ◽  
Nanda Ramchandar ◽  
Christopher Cannavino ◽  
Alice Pong ◽  
Adriana Tremoulet ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Infectious Diseases ◽  
Clinical Application ◽  
Clinical Care ◽  
Next Generation ◽  
Children's Hospital ◽  
Percent Agreement ◽  
Children’S Hospital ◽  
The Impact ◽  
Generation Sequencing

Abstract Background Children affected by infectious diseases may not always have a detectable infectious etiology. Diagnostic uncertainty can lead to prolonged hospitalizations, inappropriately broad or extended courses of antibiotics, invasive diagnostic procedures, and difficulty predicting the clinical course and outcome. Cell-free plasma next-generation sequencing (cfNGS) can identify viral, bacterial, and fungal infections by detecting pathogen DNA in peripheral blood. This testing modality offers the ability to test for many organisms at once in a shotgun metagenomic approach with a rapid turnaround time. We sought to compare the results of cfNGS to conventional diagnostic test results and describe the impact of cfNGS on clinical care in a diverse pediatric population at a large academic children’s hospital. Methods We performed a retrospective chart review of hospitalized subjects at a tertiary pediatric hospital to determine the diagnostic yield of cfNGS and its impact on clinical care. Results We describe the clinical application of results from 142 cfNGS tests in the management of 110 subjects over an 8-month study period. In comparison to conventional testing as a reference standard, cfNGS was found to have a positive percent agreement of 89.6% and negative percent agreement of 52.3%. Furthermore, 32.4% of cfNGS results were directly applied to make a clinical change in management. Conclusions We demonstrate the clinically utility of cfNGS in the management of acutely ill children. Future studies, both retrospective and prospective, are needed to clarify the optimal indications for testing.

scholarly journals Metagenomic Next-Generation Sequencing Improves the Prognosis of Patients with Infectious Diseases on Mechanical Ventilation in the Intensive Care Unit (ICU)

2020 ◽  
Author(s):  
Yin Xi ◽  
Jing Zhou ◽  
Zhimin Lin ◽  
Weibo Liang ◽  
Chun Yang ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Mechanical Ventilation ◽  
Next Generation Sequencing ◽  
Mortality Rate ◽  
Infectious Diseases ◽  
Apache Ii Score ◽  
Next Generation ◽  
Double Positive ◽  
Conventional Methods ◽  
Generation Sequencing

Abstract Background: Metagenomic Next-Generation Sequencing (mNGS) has gradually shown its advantages in pathogen identification for clinical infectious disease. However, few studies were conducted on the evaluation between this technique and conventional methods like culture and PCR and the prognosis of patients with infectious diseases on mechanical ventilation in ICUMethods: We conducted this retrospective study from March 2018 to May 2020 in the first Affiliated Hospital of Guangzhou Medical University, a total of 228 patients with suspected infectious diseases on mechanical ventilation were included, including 104 cases of mNGS group and 124 cases of non-mNGS. Statistical analyses were performed between the two groups and subgroup of whether were immunocompromised. The concordance between mNGS, culture and PCR was also assessed.Results: The 28-day mortality rate of the patients in the mNGS group was lower after the baseline difference correction (19.23% vs. 29.03%，p=0.039), indicating that mNGS may improve the prognosis of patients in ICU. And subgroup analysis showed that mNGS could improve the 28-day mortality of nonimmunosuppressive patients（14.06% vs. 29.82%, p=0.018）. According to the analysis of Logistic Regression, not performing mNGS, high APACHE II score and hypertension were independent risk factors for 28-day mortality, which strongly suggested that mNGS was one of the key factors affecting prognosis. A total of 157 samples performed mNGS, 116 of them received both mNGS and culture. mNGS presented advantages of positivity (69.8% double positive and 25.0% mNGS positive only) and concordance (79.0%, match and partly match).Conclusions: mNGS may improve the prognosis and reduce the 28-day mortality rate of patients with infectious diseases on mechanical ventilation in ICU. This technique has shown its advantages comparing with conventional methods, and will be wildly used as a promising technology for infectious disease.

scholarly journals Next-Generation Sequencing Could be a Promising Diagnostic Approach for Pathogen Detection: Pathogenic Analysis of Pediatric Bacterial Meningitis by Next-Generation Sequencing Technology Directly from Cerebrospinal Fluid Specimens

2018 ◽  
Author(s):  
Ling-yun Guo ◽  
Yong-jun Li ◽  
Lin-lin Liu ◽  
Hong-long Wu ◽  
Jia-li Zhou ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Next Generation Sequencing ◽  
Bacterial Meningitis ◽  
Infectious Diseases ◽  
Pediatric Population ◽  
Diagnostic Approach ◽  
Next Generation ◽  
Promising Alternative ◽  
Causative Microorganism ◽  
Generation Sequencing

AbstractBackgroundBacterial meningitis remains one of the major challenges in infectious diseases, leading to sequel in many cases. A prompt diagnosis of the causative microorganism is critical to significantly improve outcome of bacterial meningitis. Although various targeted tests for cerebrospinal fluid (CSF) samples are available, it is a big problem for the identification of etiology of bacterial meningitis.MethodsHere we describe the use of unbiased sequence analyses by next-generation sequencing (NGS) technology for the identification of infectious microorganisms from CSF samples of pediatric bacterial meningitis patients in the Department of Infectious Diseases from Beijing Children’s Hospital.ResultsIn total, we had 99 bacterial meningitis patients in our study, 55 (55.6%) of these were etiologically confirmed by clinical microbiology methods. Combined with NGS, 68 cases (68.7%) were etiologically confirmed. The main pathogens identified in this study were Streptococcus pneumoniae (n=29), group B streptococcus (n=15), Staphylococcus aureus (n=7), Escherichia coli (n=7). In addition, two cases with cytomegalovirus infection and one with Taenia saginata asiatica were confirmed by NGS.ConclusionsNGS could be a promising alternative diagnostic approach for critically ill patients suffering from bacterial meningitis in pediatric population.SummaryWe conducted the study for the identification of microorganisms by next-generation sequencing directly from CSF samples of pediatric bacterial meningitis patients. And the study showed that NGS could be a promising alternative diagnostic approach for bacterial meningitis in pediatric population.

scholarly journals Next-generation sequencing refines the genetic architecture of Greek GnRH-deficient patients

2019 ◽  
Vol 8 (5) ◽  
pp. 468-480 ◽  
Author(s):  
M I Stamou ◽  
P Varnavas ◽  
L Plummer ◽  
V Koika ◽  
N A Georgopoulos
Keyword(s):  
Genetic Variation ◽  
Next Generation Sequencing ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Wide Spectrum ◽  
Next Generation ◽  
Whole Exome ◽  
Low Prevalence ◽  
Generation Sequencing

Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is a rare disease with a wide spectrum of reproductive and non-reproductive clinical characteristics. Apart from the phenotypic heterogeneity, IGD is also highly genetically heterogeneous with >35 genes implicated in the disease. Despite this genetic heterogeneity, genetic enrichment in specific subpopulations has been described. We have previously described low prevalence of genetic variation in the Greek IGD cohort discovered with utilization of Sanger sequencing in 14 known IGD genes. Here, we describe the expansion of genetic screening in the largest IGD Greek cohort that has ever been studied with the usage of whole-exome sequencing, searching for rare sequencing variants (RSVs) in 37 known IGD genes. Even though Sanger sequencing detected genetic variation in 21/81 IGD patients in 7/14 IGD genes without any evidence of oligogenicity, whole exome sequencing (WES) revealed that 27/87 IGD patients carried a rare genetic change in a total of 15 genes with 4 IGD cases being oligogenic. Our findings suggest that next-generation sequencing (NGS) techniques can discover previously undetected variation, making them the standardized method for screening patients with rare and/or more common disorders.

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