The Bacterial and Viral Complexity of Infant Postinfectious Hydrocephalus in Uganda:
- The largest single cause of infant hydrocephalus worldwide is neonatal sepsis
- We uncovered a novel Paenibacillus strain as a dominant pathogen in Ugandan infants with postinfectious hydrocephalus, with a frequent co-infection with cytomegalovirus
- There are geographical location and environmental rainfall factors related to the Paenibacillus infection risk
- A predictive model for personalized point-of-care treatment optimization is being developed
Of the estimated 400,000 new cases of pediatric hydrocephalus each year, about half are estimated to be postinfectious, with the largest number of cases in low- and middle-income countries, especially sub-Saharan Africa. Neonatal sepsis often precedes postinfectious hydrocephalus (PIH). There has never been a case-controlled comprehensive evaluation of the underlying microbial agents responsible for PIH. Characterization of the microbial agents causing PIH could lead to an emphasis shift from high technology palliation of CSF accumulation to prevention.
In this study, we examined blood and CSF from 100 consecutive cases of PIH and control cases of non-postinfectious hydrocephalus (NPIH) in infants under 3 months of age at the CURE Children’s Hospital in Mbale, Uganda. Genomic testing was undertaken for bacterial, fungal, and parasitic DNA, as well as DNA and RNA sequencing for viral identification.
We uncovered a major contribution to PIH from Paenibacillus bacteria (38/64 PIH, 2/36 NPIH), upon a background of frequent cytomegalovirus (CMV) infection (18/64 PIH, 9/36 NPIH). However, CMV was only found in CSF in PIH cases (8/64). There was a significant association of the Paenibacillus infections with substantial brain destruction and calcified abscess formation. A facultatively anaerobic isolate was recovered, and assembly of the genome revealed a strain of P. thiaminolyticus. In weanling C57BL/6J mice, this isolate, designated strain Mbale, was lethal at a high dose, in contrast with the reference strain of P. thiaminolyticus.
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.
Funding: NIH Director’s Pioneer Award
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Room: Amphi Duclaux
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