DISCUSSION
Divergent strains of astroviruses are known to cause infection in humans, including classical HAstV (types 1-8), MLB and VA1 viruses.5 Studies show 90% and 65% seropositivity against classical HAstV and VA1 and close to 100% seropositivity in adulthood for MLB1 suggesting that viral exposure is common and frequent throughout life.21-24 These pathogens have recently been found to cause CNS infection mostly in immunocompromised hosts, especially VA1. Astrovirus encephalitis was first described in 2010. Since then, a total of 10 cases of astrovirus CNS infection have been reported (Table 1).9-17
All five patients with HAstV-VA1 infection were immunocompromised9,11-14 and were diagnosed with m-NGS; in only 2 cases the virus was identified before the patient died.11,13One patient was treated with ribavirin, steroids, IVIG and Peg-INF survived but recovered with cognitive and movement sequelae.11 Two of three cases with MLB encephalitis recovered fully, one was an immunocompetent host.10,15One patient with classical strain (HAstV-4) died while the other was an immunocompetent host and recovered.16,17 Hence, there seems to be variability, not only on the host characteristics but also on the virulence among strains.
We report two children who developed encephalitis with HAstV VA1 strain while undergoing treatment for leukemia. In both patients, traditional diagnostic tests were negative, and the virus was identified using m-NGS on the CSF. This unbiased technique, not limited by specific targets, enables the identification of novel pathogens.25Despite its potential, m-NGS is not routinely utilized. Considerations of costs, reimbursement, turnaround time, and regulations remain major hurdles.25 Interpretation of m-NGS can be difficult and discerning between a contaminant, colonizer or pathogen can be challenging.25
Patient 1 was managed based on the treatment outlined by Frémond et al11 which resulted in the only surviving case of VA1 encephalitis to date. Our patient was treated for about 8 months and survived. She remains with significant neuropsychiatric sequelae and dependent for activities of daily living. The extent to which she will recover neurologically remains unknown. Given the paucity of information in treating this severe infection, we attempted to optimize her treatment by including nitazoxanide, based on in vitro data19,20 and analyzing commercially available IVIG. While we observed VA1 and HAstV-1 antibodies in all IVIG lots, there was no significant differences in neutralizing activity. These results show that commercially available IVIG lots have HAstV antibodies but their role in this setting remains to be determined.
HAstV should be considered in the differential of acute encephalitis in immunosuppressed patients. m-NGS is not routinely accessible but can be vital in yielding a definitive diagnosis when conventional tests are inconclusive. We emphasize the importance of early diagnosis due to high morbidity and mortality associated with HAstV encephalitis, with potential improved outcomes with the therapy described in surviving patients. The true extent of the pathogenesis of HAstV among immunocompromised patients is unclear and needs to be elucidated with further studies.