Emerging Diagnostic and Therapeutic Tools for Central Nervous System Infections

Abstract

The field of neurological infections is constantly changing, and the emergence of new pathogens including Zika virus (ZIKV), 1 already makes earlier commentaries look dated. 2 This commentary highlights 2 important "next-generation" approaches to diagnosis and therapy that are either already clinically relevant or likely to be tested in central nervous system (CNS) neurotropic viral infections in the near future.

A novel cause of chronic viral meningoencephalitis: Cache Valley virus

“…Because CVV is rarely identified as a cause of human disease and has not been reported in Australia previously, there are no traditional candidate‐based diagnostic tests for this virus available in Australia. This unusual case highlights the ability for mNGS to identify pathogens not previously associated with a clinical phenotype and not known to circulate in a geographic area . It is also important to note that mNGS was able to identify CVV in the CSF of this patient; if these results had been available before the brain biopsy, they could have obviated the need for this invasive procedure.…”

“…Outbreaks of emerging and reemerging pathogens have stimulated international discussion about the most efficient means for improving early detection so that public and private resources can be mobilized quickly and efficiently to limit widespread transmission and treat affected patients. There is a growing consensus that an optimal surveillance regimen will (1) incorporate an unbiased approach to pathogen identification and (2) focus surveillance efforts on groups of people at high risk for unusual infections (eg, immunodeficient patients and people with relevant exposures) . An unbiased approach to pathogen identification is important because traditional candidate‐based diagnostic tests essentially fail to identify novel and unusual pathogens, usually due to perceived rarity or exclusion from clinical consideration based on established geographical distribution.…”

Metagenomics for neurological infections — expanding our imagination

“…Immunocompromised patients present particular challenges because they are susceptible to unusual neuroinvasive pathogens that might not be part of a neurologist’s standard diagnostic algorithm 2 , 10 , 17 , 23 – 26 . In addition, many emerging and re-emerging pathogens have neuroinvasive potential, including Ebola, measles, mumps, Nipah, Hendra, Chikungunya, Zika and Powassan viruses 4 , 23 , 24 , 27 – 29 . Zika virus had been circulating in Brazil for 18 months before it was identified and for 24 months before it was determined that it was responsible for a spike in cases of microcephaly and Guillain–Barré syndrome 30 .…”

Exploratory analysis of the potential for advanced diagnostic testing to reduce healthcare expenditures of patients hospitalized with meningitis or encephalitis

“…Obstacles to widespread adoption of mNGS include concerns about high costs, long turnaround time, and need for additional data about test performance characteristics. Thus, mNGS is often reserved for use as a late-stage option in diagnostically challenging cases [11][12][13][14][15][16]. Ongoing clinical validation of mNGS testing for a number of syndromes, results are based on did not include special access privileges to the data beyond the license.…”