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

A summary of the article by Greninger et al. “A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012–14): a retrospective cohort study” was published on The TMA Blog on November 6, 2015.

Breitweiser, Pardo, and Salzberg recently published an article that re-analyzed data from this study. They used data available from metagenomic shotgun sequencing to re-analyze 31 samples from the prior study published by Greninger et. al. in Lancet Infect Dis 2015; 15; 671–82. Metagenomic sequencing analysis is when DNA or RNA, the genetic material for organisms, is taken from human samples and analyzed to see if there is DNA from bacterial or viral pathogens.  The original study had looked at 48 samples from patients who went to Children’s Hospital Colorado or Children’s Hospital Los Angeles from November 24, 2013 to October 11, 2014, or individuals who were identified by the California Department of Public Health between January 1, 2012 and October 4, 2014. 25 of them were diagnosed with Acute Flaccid Myelitis (AFM), two with enterovirus-associated encephalitis (inflammation of the brain), five had enterovirus D68-associated upper respiratory illness, and 16 had aseptic meningitis or encephalitis and also tested positive for enterovirus. Breitweiser, Pardo, and Salzberg found in their re-analysis, two samples which had more sequences of bacteria than enterovirus D68. One individual without AFM had bacterial sequences from Haemophilus influenza. The other individual did have AFM, and had bacterial sequences from Staphylococcus aureus. Prior studies have shown that S. aureus may be associated with neurological problems like myelitis and meningitis. The authors suggest that while they can’t know whether these bacterial infections contributed to the two individuals’ symptoms, they argue that they should be considered as a potential factor that led to their symptoms. Furthermore, they found that the data they downloaded had a lot of human DNA in it even though the authors of the original articles stated they removed human DNA. The authors note that this is a common problem in this type of research though. The authors also stated that it is important for researchers to release gene sequencing data so that other researchers can verify the results of studies.

Original Article: Breitwieser FP, Pardo CA and Salzberg SL. Re-analysis of metagenomic sequences from acute flaccid myelitis patients reveals alternatives to enterovirus D68 infection [version 2; referees: 2 approved] F1000Research 2015, 4:180.

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