Coinfections identified from metagenomic analysis of cervical lymph nodes from tularemia patients View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-07-11

AUTHORS

D. N. Birdsell, Y. Özsürekci, A. Rawat, A. E. Aycan, C. L. Mitchell, J. W. Sahl, A. Johansson, R. E. Colman, J. M. Schupp, M. Ceyhan, P. S. Keim, D. M. Wagner

ABSTRACT

BACKGROUND: Underlying coinfections may complicate infectious disease states but commonly go unnoticed because an a priori clinical suspicion is usually required so they can be detected via targeted diagnostic tools. Shotgun metagenomics is a broad diagnostic tool that can be useful for identifying multiple microbes simultaneously especially if coupled with lymph node aspirates, a clinical matrix known to house disparate pathogens. The objective of this study was to analyze the utility of this unconventional diagnostic approach (shotgun metagenomics) using clinical samples from human tularemia cases as a test model. Tularemia, caused by the bacterium Francisella tularensis, is an emerging infectious disease in Turkey. This disease commonly manifests as swelling of the lymph nodes nearest to the entry of infection. Because swollen cervical nodes are observed from many different types of human infections we used these clinical sample types to analyze the utility of shotgun metagenomics. METHODS: We conducted an unbiased molecular survey using shotgun metagenomics sequencing of DNA extracts from fine-needle aspirates of neck lymph nodes from eight tularemia patients who displayed protracted symptoms. The resulting metagenomics data were searched for microbial sequences (bacterial and viral). RESULTS: F. tularensis sequences were detected in all samples. In addition, we detected DNA of other known pathogens in three patients. Both Hepatitis B virus (HBV) and Human Parvovirus B-19 were detected in one individual and Human Parvovirus B-19 alone was detected in two other individuals. Subsequent PCR coupled with Sanger sequencing verified the metagenomics results. The HBV status was independently confirmed via serological diagnostics, despite evading notice during the initial assessment. CONCLUSION: Our data highlight that shotgun metagenomics of fine-needle lymph node aspirates is a promising clinical diagnostic strategy to identify coinfections. Given the feasibility of the diagnostic approach demonstrated here, further steps to promote integration of this type of diagnostic capability into mainstream clinical practice are warranted. More... »

PAGES

319

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12879-018-3218-2

DOI

http://dx.doi.org/10.1186/s12879-018-3218-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105470933

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29996780


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26 schema:description BACKGROUND: Underlying coinfections may complicate infectious disease states but commonly go unnoticed because an a priori clinical suspicion is usually required so they can be detected via targeted diagnostic tools. Shotgun metagenomics is a broad diagnostic tool that can be useful for identifying multiple microbes simultaneously especially if coupled with lymph node aspirates, a clinical matrix known to house disparate pathogens. The objective of this study was to analyze the utility of this unconventional diagnostic approach (shotgun metagenomics) using clinical samples from human tularemia cases as a test model. Tularemia, caused by the bacterium Francisella tularensis, is an emerging infectious disease in Turkey. This disease commonly manifests as swelling of the lymph nodes nearest to the entry of infection. Because swollen cervical nodes are observed from many different types of human infections we used these clinical sample types to analyze the utility of shotgun metagenomics. METHODS: We conducted an unbiased molecular survey using shotgun metagenomics sequencing of DNA extracts from fine-needle aspirates of neck lymph nodes from eight tularemia patients who displayed protracted symptoms. The resulting metagenomics data were searched for microbial sequences (bacterial and viral). RESULTS: F. tularensis sequences were detected in all samples. In addition, we detected DNA of other known pathogens in three patients. Both Hepatitis B virus (HBV) and Human Parvovirus B-19 were detected in one individual and Human Parvovirus B-19 alone was detected in two other individuals. Subsequent PCR coupled with Sanger sequencing verified the metagenomics results. The HBV status was independently confirmed via serological diagnostics, despite evading notice during the initial assessment. CONCLUSION: Our data highlight that shotgun metagenomics of fine-needle lymph node aspirates is a promising clinical diagnostic strategy to identify coinfections. Given the feasibility of the diagnostic approach demonstrated here, further steps to promote integration of this type of diagnostic capability into mainstream clinical practice are warranted.
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33 schema:keywords B virus
34 DNA
35 DNA extracts
36 Francisella tularensis
37 HBV status
38 PCR
39 Sanger sequencing
40 Turkey
41 addition
42 analysis
43 approach
44 aspirates
45 assessment
46 bacterium Francisella tularensis
47 broad diagnostic tool
48 capability
49 cases
50 cervical lymph nodes
51 cervical nodes
52 clinical diagnostic strategy
53 clinical matrices
54 clinical practice
55 clinical sample types
56 clinical samples
57 clinical suspicion
58 coinfection
59 data
60 data highlight
61 diagnostic approach
62 diagnostic capabilities
63 diagnostic strategies
64 diagnostic tool
65 diagnostics
66 different types
67 disease
68 disease states
69 disparate pathogens
70 entry
71 entry of infection
72 extract
73 feasibility
74 fine needle aspirates
75 fine-needle lymph node aspirates
76 further step
77 hepatitis B virus
78 highlights
79 human infections
80 human parvovirus B
81 human tularemia cases
82 individuals
83 infection
84 infectious disease states
85 infectious diseases
86 initial assessment
87 integration
88 lymph node aspirates
89 lymph nodes
90 lymph nodes nearest
91 mainstream clinical practice
92 matrix
93 metagenomic analysis
94 metagenomic data
95 metagenomic results
96 metagenomic sequencing
97 metagenomics
98 microbes
99 microbial sequences
100 model
101 molecular survey
102 multiple microbes
103 nearest
104 neck lymph nodes
105 node aspirates
106 nodes
107 nodes nearest
108 notice
109 objective
110 parvovirus B
111 pathogens
112 patients
113 practice
114 promising clinical diagnostic strategy
115 results
116 sample types
117 samples
118 sequence
119 sequencing
120 serological diagnostics
121 shotgun metagenomic sequencing
122 shotgun metagenomics
123 state
124 status
125 step
126 strategies
127 study
128 subsequent PCR
129 survey
130 suspicion
131 swollen cervical nodes
132 symptoms
133 test model
134 tool
135 tularemia
136 tularemia cases
137 tularemia patients
138 tularensis
139 tularensis sequences
140 types
141 unbiased molecular survey
142 unconventional diagnostic approach
143 utility
144 virus
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