Research ArticleInfectious Disease

Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants

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Science Translational Medicine  30 Sep 2020:
Vol. 12, Issue 563, eaba0565
DOI: 10.1126/scitranslmed.aba0565

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Hydrocephalus is a serious brain disorder in children and the most common indication for pediatric neurosurgery. Worldwide, the most frequent cause of hydrocephalus is previous infection such as neonatal sepsis. Such postinfectious hydrocephalus (PIH) occurs principally in low- and middle-income countries, and the pathogens responsible remain uncharacterized. Paulson et al. used pan-microbial analysis of CSF samples from infants with PIH in Uganda to identify the bacteria, viruses, fungi, or parasites potentially contributing to PIH. They found a new strain of the bacterium Paenibacillus as well as frequent coinfection with cytomegalovirus as contributors to PIH in this infant cohort.

Abstract

Postinfectious hydrocephalus (PIH), which often follows neonatal sepsis, is the most common cause of pediatric hydrocephalus worldwide, yet the microbial pathogens underlying this disease remain to be elucidated. Characterization of the microbial agents causing PIH would enable a shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention of the disease. Here, we examined blood and CSF samples collected from 100 consecutive infant cases of PIH and control cases comprising infants with non-postinfectious hydrocephalus in Uganda. Genomic sequencing of samples was undertaken to test for bacterial, fungal, and parasitic DNA; DNA and RNA sequencing was used to identify viruses; and bacterial culture recovery was used to identify potential causative organisms. We found that infection with the bacterium Paenibacillus, together with frequent cytomegalovirus (CMV) coinfection, was associated with PIH in our infant cohort. Assembly of the genome of a facultative anaerobic bacterial isolate recovered from cultures of CSF samples from PIH cases identified a strain of Paenibacillus thiaminolyticus. This strain, designated Mbale, was lethal when injected into mice in contrast to the benign reference Paenibacillus strain. These findings show that an unbiased pan-microbial approach enabled characterization of Paenibacillus in CSF samples from PIH cases, and point toward a pathway of more optimal treatment and prevention for PIH and other proximate neonatal infections.

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