The Bacterial and Viral Complexity of Postinfectious Hydrocephalus in Uganda

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Paulson, Joseph, Williams, Brent, Hehnly, Christine ORCID: 0000-0003-3739-0690, Mishra, Nischay, Sinnar, Shamim, Zhang, Lijun, Ssentongo, Paddy, Mbabazi-Kabachelor, Edith, Wijetunge, Dona, von Bredow, Benjamin et al (show 42 more authors) , Mulondo, Ronnie ORCID: 0000-0003-2672-3162, Kiwanuka, Julius, Bajunirwe, Francis, Bazira, Joel, Bebell, Lisa, Burgoine, Kathy, Couto-Rodriguez, Mara, Ericson, Jessica, Erickson, Tim, Ferrari, Matthew, Gladstone, Melissa ORCID: 0000-0002-2579-9301, Guo, Cheng, Haran, Murali, Hornig, Mady, Isaacs, Albert, Kaaya, Brian Nsubuga, Kangere, Sheila, Kulkarni, Abhaya, Kumbakumba, Elias, Li, Xiaoxiao, Limbrick, David, Magombe, Joshua, Morton, Sarah, Mugamba, John, Ng, James, Olupot-Olupot, Peter, Onen, Justin, Peterson, Mallory, Roy, Farrah, Sheldon, Kathryn, Townsend, Reid, Weeks, Andrew ORCID: 0000-0002-1909-337X, Whalen, Andrew, Quackenbush, John, Ssenyonga, Peter, Galperin, Michael ORCID: 0000-0002-2265-5572, Almeida, Mathieu, Atkins, Hannah, Warf, Benjamin, Lipkin, Ian, Broach, James and Schiff, Steven (2020) The Bacterial and Viral Complexity of Postinfectious Hydrocephalus in Uganda Science Translational Medicine. 2020.08.03.20167544-. ISSN 1946-6234

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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. <h4>One Sentence Summary</h4> We have discovered a novel strain of bacteria upon a frequent viral background underlying postinfectious hydrocephalus in Uganda.

Item Type:	Article
Uncontrolled Keywords:	3107 Microbiology, 3207 Medical Microbiology, 32 Biomedical and Clinical Sciences, 31 Biological Sciences, Pediatric Research Initiative, Infant Mortality, Perinatal Period - Conditions Originating in Perinatal Period, Neurosciences, Brain Disorders, Hematology, Hydrocephalus, Infectious Diseases, Biodefense, Sepsis, Genetics, Emerging Infectious Diseases, Rare Diseases, Prevention, 2.1 Biological and endogenous factors, Infection, 3 Good Health and Well Being
Depositing User:	Symplectic Admin
Date Deposited:	10 Feb 2020 10:20
Last Modified:	15 Jan 2026 19:21
DOI:	10.1101/2020.08.03.20167544
Related Websites:	Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3073907
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