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.