Paenibacillus Infection Causes Neonatal Sepsis and Subsequent Postinfectious Hydrocephalus in Ugandan Infants

Background: Paenibacillus thiaminolyticus was identified as an important contributor to postinfectious hydrocephalus (PIH) among Ugandan infants as a sequela from prior neonatal sepsis (NS). To better determine the significance of this organism’s role in NS and PIH, we complete separate studies of Ugandan with hydrocephalus, with and without prior evidence of infection (case-control), as well as neonates with sepsis (observational cohort), and maternal-newborn pairs (case-control, with and without maternal fever). Methods: From 2016-2019, 400 infants with hydrocephalus were recruited. 16S rDNA sequencing was used to characterize the bacterial content of infant cerebrospinal fluid (CSF). One hundred maternal-newborn pairs and 800 neonates with sepsis were recruited. Two quantitative polymerase chain reactions (qPCR) targeting either the Paenibacillus genus or Paenibacillus thiaminolyticus species of all 2578 specimens were performed. In addition, cranial ultrasound and computed tomography images were collected.Findings: Paenibacillus was the most enriched bacterial genera in PIH CSF (44%), with 16S demonstrating 94% accuracy when validated by qPCR. No Paenibacillus was detected in vaginal, maternal blood, placental or cord blood specimens. Paenibacillus was detected in 5% of septic neonates, and of these 19% developed PIH. Imaging demonstrated progression from Paenibacillus meningitis to PIH over months. PIH patients with Paenibacillus infections were geographically clustered. Interpretation: Paenibacillus causes neonatal sepsis and meningitis in Uganda, and is the dominant cause of subsequent PIH. There was no evidence of transplacental transmission, and geographical evidence was consistent with an environmental source of neonatal infection. Further work is needed to identify routes of infection and optimize treatment of neonatal Paenibacillus infection to lessen the burden of morbidity and mortality.Funding: The National Institutes of Health (NIH) Director’s Pioneer Award 5DP1HD086071 and NIHDirector’s Transformative Award 1R01AI145057 to SJS, and Boston Children’s Hospital Officeof Faculty Development Career Development Award to SUM.Declaration of Interest: None to declare. Ethical Approval: Ethics oversight was provided by the CURE Children's Hospital of Uganda (CCHU) Institutional Review Board, Mbarara University of Science and Technology Research Ethics Committee, Ugandan National Council on Science and Technology, and Pennsylvania State University Institutional Review Board.