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Scientists discover bacterium linked to post-infectious hydrocephalus (PIH)

Scientists at the Center for Infection and Immunity (CII) at Columbia University Mailman School of Public Health have discovered bacteria 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 the journal Science Translational Medicine.

Hydrocephalus is the most common indication for neurosurgery in children. Of the estimated 400,000 new cases each year, about half are estimated to be post-infectious, with the largest number of cases in low- and middle-income countries, especially sub-Saharan Africa.

Neonatal sepsis often precedes PIH, although the manifestations of hydrocephalus typically emerge in the months following the neonatal period as cerebrospinal fluid accumulates so that cranial expansion garners medical attention. These infants typically die in early childhood without advanced surgical management.


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Study co-first author Brent L. Williams, PhD, assistant professor of epidemiology at CII, examined cerebrospinal fluid (CSF) taken from 100 consecutive cases of PIH and control cases of non-post-infectious hydrocephalus (NPIH) in infants in Uganda, testing the samples for evidence of bacterial and fungal microorganisms.

He found Paenibacillus species (bacteria) in CSF linked to cases of PIH, not controls. Williams further quantitated Paenibacillus species in infant CSF samples, finding a high burden of these bacteria in infected patients.

The findings were subsequently independently confirmed, and a strain of Paenibacillus was isolated and characterized through further testing by Steven Schiff, MD, the study’s senior author, and colleagues at Pennsylvania State University. The researchers also found 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.

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Co-senior author W. Ian Lipkin, MD, John Snow Professor and CII Director, noted that “this 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.”


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“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 Brent Williams.

Source:

Columbia University’s Mailman School of Public Health

Journal Reference:

Paenibacillus infection with frequent viral coinfection contributes to post-infectious hydrocephalus in Ugandan infants

Abstract:
Post-infectious 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-post-infectious 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.


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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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