A novel cause of chronic viral meningoencephalitis: Cache Valley virus

Wilson, Michael R.; Suan, Dan; Duggins, Andrew; Schubert, Ryan D.; Khan, Lillian M.; Sample, Hannah A.; Zorn, Kelsey C.; Rodrigues Hoffman, Aline; Blick, Anna; Shingde, Meena; DeRisi, Joseph L.

Whereas CVV is widespread throughout North and South America, it and other members of the Bunyamwera serogroup have not been previously detected in Australia. 22 Given that CVV is a mosquito-borne virus that can be carried by at least 33 species of mosquitoes across 7 genera, there are likely mosquito species competent to transmit CVV in Australia. 38, 39 Although we have no evidence that wider transmission has occurred, it is plausible that our subject could have transmitted CVV to mosquitos in Australia during the 3-year period since his return from the United States. The possibility of having introduced a mosquitoborne virus to a new locale is made even more salient by the recent international Zika virus crisis. The spread of Zika to Latin America was in part exacerbated by the delayed recognition of its introduction to Brazil. Recent phylogenetic studies have indicated that Zika virus was circulating for 18 months before it was identified as a pathogen, and for 24 months before it was determined that Zika was likely responsible for the recent increase in the incidence of microcephaly. 40 The most dramatic example of a virus spreading undetected among human populations over many decades remains HIV-1. 41 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. 2, 3 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. The ability to identify unanticipated infections in CSF via mNGS in this patient and others motivates the ongoing prospective, multicenter study currently underway to determine the performance characteristics of an mNGS CSF assay performed in a clinical laboratory environment for patients with acute meningitis with or without encephalitis (http://www. ciapm.org/project/precision-diagnosis-acute-infectious-diseases). When applied more broadly to global pathogen surveillance efforts, mNGS will significantly enhance the detection and monitoring of global biothreats. Finally, this case extends the spectrum of viruses known to cause chronic meningoencephalitis.