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

Ramesh, A.; Nakielny, S.; Hsu, J.; Kyohere, M.; Byaruhanga, O.; de Bourcy, C.; Egger, R.; Dimitrov, B.; Juan, Y.-F.; Sheu, J.; Wang, J.; Kalantar, K.; Langelier, C.; Ruel, T.; Mpimbaza, A.; Wilson, M. R.; Rosenthal, P. J.; DeRisi, J. L.

doi:10.1101/385005

bioRxiv · 10.1101/385005

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

Ramesh, A.·Nakielny, S.·Hsu, J.·Kyohere, M.·Byaruhanga, O.·de Bourcy, C.·Egger, R.·Dimitrov, B.·Juan, Y.-F.·Sheu, J.·Wang, J.·Kalantar, K.·Langelier, C.·Ruel, T.·Mpimbaza, A.·Wilson, M. R.·Rosenthal, P. J.·DeRisi, J. L.

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Abstract

BackgroundFebrile 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.\n\nResultsThe 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.\n\nConclusionsThis 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.

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Ramesh, A., Nakielny, S., Hsu, J., Kyohere, M., Byaruhanga, O., de Bourcy, C., Egger, R., Dimitrov, B., Juan, Y.-F., Sheu, J., Wang, J., Kalantar, K., Langelier, C., Ruel, T., Mpimbaza, A., Wilson, M. R., Rosenthal, P. J., DeRisi, J. L.. 2018-08-04. Etiology of fever in Ugandan children: identification of microbial pathogens using metagenomic next-generation sequencing and IDseq, a platform for unbiased metagenomic analysis. https://doi.org/10.1101/385005

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