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Post-Infectious Hydrocephalus in Ugandan Children Traced Back to Bacterial, Viral Pathogens

NEW YORK – An international team of researchers has used genomic sequencing and other approaches to identify a new bacterial strain and a common virus in Ugandan children with post-infectious hydrocephalus.

Hydrocephalus, the buildup of fluid in brain cavities, affects about 400,000 children a year, particularly in sub-Saharan Africa, and about half the cases are caused by neonatal infections. 

To determine the infectious agents contributing to post-infectious hydrocephalus, an international team of researchers sequenced cerebrospinal fluid and blood samples from infants with and without the condition who were seen at a Ugandan hospital. As the researchers reported on Wednesday in Science Translational Medicine, they uncovered a novel strain of the bacterium Paenibacillus thiaminolyticus in conjunction with cytomegalovirus among affected children. 

"Hydrocephalus is the most common childhood neurosurgical condition that we see in the population that we serve," Edith Mbabazi-Kabachelor, director of research at CURE Children's Hospital of Uganda (CCHU) in Mbale, said in a statement. "If hydrocephalus is left untreated in children less than two years old, the progressive increase in head size will lead to further brain damage, resulting in the majority of these children dying, and those that survive being left with severe cognitive and physical disability."

The researchers analyzed samples from 100 patients, 64 with post-infectious hydrocephalus and 36 with non-post-infectious hydrocephalus, all of whom were less than three months old and were seen at CCHU. Using both Sanger-based sequencing of bacterial 16S ribosomal DNA V1-V4 regions and next-generation sequencing of the V1-V2 and V4 regions, the researchers homed in on Paenibacillus among samples from affected but not from unaffected children.

A number of clinical measures such as white blood cell counts in cerebrospinal fluid and CT scan results were associated with the presence of Paenibacillus.

As other diseases have both bacterial and viral elements, the researchers additionally searched for genetic material from viruses, fungi, and parasites in their patient samples. Using a targeted viral detection capture approach called VirCapSeqVERT, they uncovered 11 viral strains across slightly more than a third of CSF samples. Cytomegalovirus was found among a portion of post-infectious hydrocephalus patients' CSF samples, but not among non-post-infectious hydrocephalus patients. Cytomegalovirus is a common virus that typically causes minor symptoms in adults but may lead to neurological damage in infants who acquire it early in life.

The researchers grew three Paenibacillus isolates in culture and used whole-genome sequencing analysis to identify them as P. thiaminolyticus. They dubbed this strain Mbale after the town where the hospital is. 

Testing in mice found that the Mbale strain, unlike the reference P. thiaminolyticus strain, led to sickness in all 16 of the mice infected. Antibiotic sensitivity testing, though, revealed that the Mbale strain is broadly sensitive to common antibiotics. 

But where infants encounter the bacteria is unclear, the researchers noted. They suspect that the Mbale strain may be soil- or water-borne and are conducting additional studies to find out, including whether rainfall in the region has an effect on disease.

The researchers added that it's not known whether this combination of bacteria and virus may be behind similar infections in other regions of the world. They noted that an investigative strategy like theirs could be used to study similar infections elsewhere. 

"Both care and prevention fit within an economic framework that will help plan the optimal apportionment of healthcare funds between treatment and prevention, so that the health of these infants is best addressed," Mbabazi-Kabachelor said. "These strategies will help guide optimal use of resources for better long-term patient outcomes."