1. The Bacterial and Viral Complexity of Postinfectious Hydrocephalus in Uganda
- Author
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R. Reid Townsend, W. Ian Lipkin, Xiaoxiao Li, James Ng, Albert M. Isaacs, Sheila M. Kangere, Lisa M. Bebell, Kathy Burgoine, Edith Mbabazi-Kabachelor, Timothy B. Erickson, Peter Ssenyonga, Joel Bazira, Steven J. Schiff, Benjamin C. Warf, Julius Kiwanuka, James R. Broach, Brian Nsubuga Kaaya, Hannah M Atkins, Andrew Whalen, Dona Saumya S. Wijetunge, Paddy Ssentongo, David D. Limbrick, John Mugamba, Kathryn Sheldon, Joshua Magombe, Nishay Mishra, Abhaya V. Kulkarni, Mady Hornig, Benjamin von Bredow, Ronald Mulando, Murali Haran, Farrah Roy, Mathieu Almeida, Melissa Gladstone, Sarah U. Morton, John Quackenbush, Francis Bajunirwe, Mara Curto-Rodriguez, Mallory R. Peterson, Andrew Weeks, Christine Hehnly, Joseph N. Paulson, Cheng Guo, Michael Y. Galperin, Lijun Zhang, Jessica E. Ericson, Brent L. Williams, Justin Onen, Peter Olupot-Olupot, Shamim A. Sinnar, Elias Kumbakumba, and Matthew J. Ferrari
- Subjects
Microbiological culture ,biology ,Neonatal sepsis ,business.industry ,Congenital cytomegalovirus infection ,medicine.disease ,biology.organism_classification ,Genome ,Viral Identification ,Article ,Hydrocephalus ,Microbiology ,Cerebrospinal fluid ,medicine ,business ,Bacteria - Abstract
Postinfectious hydrocephalus (PIH), often following neonatal sepsis, is the most common cause of pediatric hydrocephalus world-wide, yet the microbial pathogens remain uncharacterized. Characterization of the microbial agents causing PIH would lead to an emphasis shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention. We examined blood and CSF from 100 consecutive cases of PIH and control cases of non-postinfectious hydrocephalus (NPIH) in infants in Uganda. Genomic testing was undertaken for bacterial, fungal, and parasitic DNA, DNA and RNA sequencing for viral identification, and extensive bacterial culture recovery. We uncovered a major contribution to PIH from Paenibacillus, upon a background of frequent cytomegalovirus (CMV) infection. CMV was only found in CSF in PIH cases. A facultatively anaerobic isolate was recovered. Assembly of the genome revealed a strain of P. thiaminolyticus. In mice, this isolate designated strain Mbale, was lethal in contrast with the benign reference strain. These findings point to the value of an unbiased pan-microbial approach to characterize PIH in settings where the organisms remain unknown, and enables a pathway towards more optimal treatment and prevention of the proximate neonatal infections.One Sentence SummaryWe have discovered a novel strain of bacteria upon a frequent viral background underlying postinfectious hydrocephalus in Uganda.
- Published
- 2020