Paenibacillus linked to hydrocephalus

NEW YORK—Scientists at the Center for Infection and Immunity (CII) at Columbia University Mailman School of Public Health have discovered that Paenibacillus is linked to post-infectious hydrocephalus (PIH), the most common cause of pediatric hydrocephalus worldwide. Results of the study, led by Pennsylvania State University with CII scientists and clinical colleagues in Uganda, are published in Science Translational Medicine.

Hydrocephalus is the most common reason for neurosurgery in children. Of the estimated 400,000 new cases each year, around half are thought to be post-infectious — with the largest number of cases in low- and middle-income countries, especially sub-Saharan Africa. Neonatal sepsis can often precede PIH, although the manifestations of hydrocephalus typically emerge in the months following the neonatal period, as cerebrospinal fluid accumulates and cranial expansion garners medical attention. These infants typically die in early childhood without advanced surgical management.

Study co-first author Brent L. Williams, Ph.D., assistant professor of epidemiology at CII, examined cerebrospinal fluid and tested the samples for evidence of bacterial and fungal microorganisms. He found Paenibacillus species in cerebrospinal fluid (CSF) linked to cases of PIH, not controls.

“In this study, we examined blood and CSF samples from 100 consecutive cases of PIH and control cases of non-post-infectious hydrocephalus in infants under 3 months of age at the CURE Children’s Hospital of Uganda in Mbale, Uganda,” says the article. “Since 2001, this pediatric neurosurgical hospital has treated thousands of cases of PIH and NPIH, with nearly uniform negative recovery of putative pathogens through standard bacterial culture. Here, we conducted molecular analysis of high-quality blood and CSF samples and undertook comprehensive testing for bacterial, fungal, and parasitic DNA; genomic and RNA transcript sequencing for viruses; and extensive bacterial culture recovery for taxonomic identification, genome assembly, and virulence characterization.”

“Our pan-microbial approach uncovered the presence of a difficult-to-grow pathogen, P. thiaminolyticus Mbale, not previously known to be virulent. This organism was associated with calcified loculations and brain abscesses in infants with PIH, as well as with hydrocephalus after survival from neonatal sepsis,” continues the article. “The organism was present on a neurotropic viral background of CMV [cytomegalovirus] infection: 6 of 8 CSF samples and 11 of 27 blood samples from our PIH infant cohort were coinfected with CMV and Paenibacillus spp.”

Williams further quantitated Paenibacillus species in infant CSF samples, finding a high burden of these bacteria in infected patients. The findings were confirmed independently, and a strain of

Paenibacillus was isolated and characterized through further testing by Steven Schiff, M.D., the study’s senior author, and colleagues at Pennsylvania State University. The researchers also found out that Paenibacillus quantity was associated with clinical measures of hydrocephalus based on brain imaging scores, as well as potential signs of infection based on immune cell counts in patients.

“[T]his discovery has the potential to reduce morbidity and mortality of this central nervous system disease in millions of children in sub-Saharan Africa by shifting treatment from surgery to antibiotics and vaccines,” pointed out co-senior author W. Ian Lipkin, M.D., and John Snow, professor and CII director.

“Now that we have identified a pathogen that may be responsible for some cases of post-infectious hydrocephalus, we can develop new, more sensitive tests to quickly detect an infection, assess its severity, identify the source of such infections and hopefully provide targeted treatments to prevent the development of hydrocephalus,” added Williams.