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Re-analysis of metagenomic sequences from acute flaccid myelitis patients reveals alternatives to enterovirus D68 infection.

Breitwieser FP, Pardo CA, Salzberg SL - F1000Res (2015)

Bottom Line: We re-analyzed metagenomic RNA sequence data collected during a recent outbreak of acute flaccid myelitis (AFM), caused in some cases by infection with enterovirus D68.We found that among the patients whose symptoms were previously attributed to enterovirus D68, one patient had clear evidence of infection with Haemophilus influenzae, and a second patient had a severe Staphylococcus aureus infection caused by a methicillin-resistant strain.These observations may have relevance in cases that present with flaccid paralysis because bacterial infections, co-infections or post-infection immune responses may trigger pathogenic processes that may present as poliomyelitis-like syndromes and may mimic AFM.  A separate finding was that large numbers of human sequences were present in each of the publicly released samples, although the original study reported that human sequences had been removed before deposition.

View Article: PubMed Central - PubMed

Affiliation: Center for Computational Biology, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.

ABSTRACT
Metagenomic sequence data can be used to detect the presence of infectious viruses and bacteria, but normal microbial flora make this process challenging. We re-analyzed metagenomic RNA sequence data collected during a recent outbreak of acute flaccid myelitis (AFM), caused in some cases by infection with enterovirus D68. We found that among the patients whose symptoms were previously attributed to enterovirus D68, one patient had clear evidence of infection with Haemophilus influenzae, and a second patient had a severe Staphylococcus aureus infection caused by a methicillin-resistant strain. Neither of these bacteria were identified in the original study. These observations may have relevance in cases that present with flaccid paralysis because bacterial infections, co-infections or post-infection immune responses may trigger pathogenic processes that may present as poliomyelitis-like syndromes and may mimic AFM.  A separate finding was that large numbers of human sequences were present in each of the publicly released samples, although the original study reported that human sequences had been removed before deposition.

No MeSH data available.


Related in: MedlinePlus

Depth of read coverage of theS. aureus MRSA252 genome using reads identified in the NGS sample from subject US/CA/12-5837.High peaks correspond to 16S rRNA genes. Red line: median coverage; blue line: mean coverage.
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f1: Depth of read coverage of theS. aureus MRSA252 genome using reads identified in the NGS sample from subject US/CA/12-5837.High peaks correspond to 16S rRNA genes. Red line: median coverage; blue line: mean coverage.

Mentions: In a second subject, US/CA/12-5837, we found a strikingly large number of reads fromStaphylococcus aureus in the NP swabs. The two separate NGS files associated with this subject contained 6,858,453 and 1,343,806 reads, comprising 70% and 84% (respectively) of all non-human reads identified at the species level in each sample. The closest match wasS. aureus subsp.aureus MRSA252, a methicillin-resistant strain. The coverage was deep enough, approximately 40X, that it would be possible to assemble this genome separately from the reads here (Figure 1). Greningeret al.2 reported 2,790 reads from enterovirus D68 in this subject (our analysis found 1,641) but did not report any fromS. aureus.


Re-analysis of metagenomic sequences from acute flaccid myelitis patients reveals alternatives to enterovirus D68 infection.

Breitwieser FP, Pardo CA, Salzberg SL - F1000Res (2015)

Depth of read coverage of theS. aureus MRSA252 genome using reads identified in the NGS sample from subject US/CA/12-5837.High peaks correspond to 16S rRNA genes. Red line: median coverage; blue line: mean coverage.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4536609&req=5

f1: Depth of read coverage of theS. aureus MRSA252 genome using reads identified in the NGS sample from subject US/CA/12-5837.High peaks correspond to 16S rRNA genes. Red line: median coverage; blue line: mean coverage.
Mentions: In a second subject, US/CA/12-5837, we found a strikingly large number of reads fromStaphylococcus aureus in the NP swabs. The two separate NGS files associated with this subject contained 6,858,453 and 1,343,806 reads, comprising 70% and 84% (respectively) of all non-human reads identified at the species level in each sample. The closest match wasS. aureus subsp.aureus MRSA252, a methicillin-resistant strain. The coverage was deep enough, approximately 40X, that it would be possible to assemble this genome separately from the reads here (Figure 1). Greningeret al.2 reported 2,790 reads from enterovirus D68 in this subject (our analysis found 1,641) but did not report any fromS. aureus.

Bottom Line: We re-analyzed metagenomic RNA sequence data collected during a recent outbreak of acute flaccid myelitis (AFM), caused in some cases by infection with enterovirus D68.We found that among the patients whose symptoms were previously attributed to enterovirus D68, one patient had clear evidence of infection with Haemophilus influenzae, and a second patient had a severe Staphylococcus aureus infection caused by a methicillin-resistant strain.These observations may have relevance in cases that present with flaccid paralysis because bacterial infections, co-infections or post-infection immune responses may trigger pathogenic processes that may present as poliomyelitis-like syndromes and may mimic AFM.  A separate finding was that large numbers of human sequences were present in each of the publicly released samples, although the original study reported that human sequences had been removed before deposition.

View Article: PubMed Central - PubMed

Affiliation: Center for Computational Biology, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.

ABSTRACT
Metagenomic sequence data can be used to detect the presence of infectious viruses and bacteria, but normal microbial flora make this process challenging. We re-analyzed metagenomic RNA sequence data collected during a recent outbreak of acute flaccid myelitis (AFM), caused in some cases by infection with enterovirus D68. We found that among the patients whose symptoms were previously attributed to enterovirus D68, one patient had clear evidence of infection with Haemophilus influenzae, and a second patient had a severe Staphylococcus aureus infection caused by a methicillin-resistant strain. Neither of these bacteria were identified in the original study. These observations may have relevance in cases that present with flaccid paralysis because bacterial infections, co-infections or post-infection immune responses may trigger pathogenic processes that may present as poliomyelitis-like syndromes and may mimic AFM.  A separate finding was that large numbers of human sequences were present in each of the publicly released samples, although the original study reported that human sequences had been removed before deposition.

No MeSH data available.


Related in: MedlinePlus