Dual infection with hepatitis A and E virus presenting with aseptic meningitis: a case report.

Abstract

We report the case of a young male who presented with features of aseptic meningitis and elevated serum liver enzymes, but no symptoms or signs suggestive of an acute hepatitis. Subsequently, he was diagnosed with dual infection with hepatitis A and E viruses, and recovered completely with symptomatic therapy. Isolated aseptic meningitis, unaccompanied by hepatitic features is an unusual presentation of a hepatotrophic viral infection, and is yet to be reported with hepatitis A and E virus co-infection.

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Asian Pacific Journal of Tropical Medicine (2012)587-588
Document heading doi: 10.1016/S1995-7645(12)60104-7
Dual infection with hepatitis A and E virus presenting with aseptic
meningitis: A case report
Kushal Naha
＊, Suman Karanth, Mukhyaprana Prabhu, Manpreet Singh Sidhu
Department of Medicine, Kasturba Hospital, Manipal-576 104, Karnataka, India
Contents lists available at ScienceDirect
Asian Pacific Journal of Tropical Medicine
journal homepage:www.elsevier.com/locate/apjtm
ARTICLE INFO ABSTRACT
Article history:
Received 10 November 2011
Received in revised form 15 January 2012
Accepted 15 March 2012
Available online 20 July 2012
Keywords:
Dual infection
Hepatitis A
Hepatitis E
Aseptic meningitis
Atypical presentation
*Corresponding author: Kushal Naha, Department of Medicine, Kasturba Medical
College, Manipal- 576 104, Karnataka, India
Email: kushalnaha@gmail.com
1. Introduction
Dual infection with hepatitis A and E virus is a potentially
under-reported condition, especially from the developing
world in the absence of adequate laboratory facilities. A
Cuban study by Lay et al[1], demonstrated such co-infection
in up to 12.8% of epidemic and sporadic cases of acute viral
hepatitis. Such a figure is not unsurprising, considering
the similar epidemiological profile of these viruses, both
sharing an enteric route of transmission. Unfortunately, data
on whether and how such cases of dual infection differ from
mono-infection with hepatitis A and E in terms of clinical
presentation and natural history are lacking.
2. Case report
A 33-year-old Asian Indian male with no premorbid
illnesses presented with high-grade fever since the past 15
days, associated with chills and rigors. He also complained
of severe holocranial headache, recurrent vomiting and mild
photophobia since the past five days. He denied any history
of substance abuse.
General physical examination revealed conjunctival
suffusion, and a fever of 102 °F. Neurological evaluation
showed grade 1 nystagmus to the left and minimal ataxia in
the left upper limb. Although nuchal rigidity was present,
Kernig’s and Brudzinski’s sign could not be elicited.
Examination of other systems was normal.
Preliminary blood investigations showed hepatitis (serum
AST 142 U/L, serum ALT 400 U/L, serum ALP 403 U/L) and
elevated total leucocyte count (13 100/mm
imaging was performed as the patient had focal neurological
deficits and was a normal study. A lumbar puncture was
done; cerebrospinal fluid (CSF) analysis revealed lymphocytic
pleiocytosis (80 cells/mm
protein (86 mg/dL). CSF glucose was normal (69 mg/dL).
Gram staining showed occasional pus cells but no
organisms; culture remained sterile. Fluorescein stain was
negative for acid fast bacilli, and polymerase chain reaction
Pending results of serological tests to determine the cause
of fever, the patient was empirically initiated on parenteral
ceftriaxone (2 g IV q12H), considering a possibility of early
pyogenic meningitis. Subsequently, the patient tested
positive for both hepatitis A and hepatitis E virus infection
by ELISA method. Simultaneously, evaluation for malaria,
leptospirosis and enteric fever was negative. Blood cultures
drawn at admission, as well as in the course of hospital stay
3). Cranial MRI
3, 90% lymphocytes), and elevated
(PCR) was negative for tuberculosis.
We report the case of a young male who presented with features of aseptic meningitis and
elevated serum liver enzymes, but no symptoms or signs suggestive of an acute hepatitis.
Subsequently, he was diagnosed with dual infection with hepatitis A and E viruses, and recovered
completely with symptomatic therapy. Isolated aseptic meningitis, unaccompanied by hepatitic
features is an unusual presentation of a hepatotrophic viral infection, and is yet to be reported
with hepatitis A and E virus co-infection.

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were persistently sterile.
In the absence of an alternative etiology, the CSF picture
of aseptic meningitis was attributed to dual infection with
hepatitis A and E viruses. Antibiotic therapy was therefore
discontinued. The patient was kept under observation, and
reported steady subjective improvement. Serial monitoring
of liver function tests and leucocyte counts showed complete
recovery.
3. Discussion
Hepatitis A infection has been linked in sporadic reports
with a range of neurological manifestations including
meningoencephalitis, acute disseminated encephalomyelitis
and peripheral neuropathy[7]. In children, hepatitis
A infection has been reported in association with
pseudotumour cerebri[8] and abducens and palatal palsy[9].
Davoudi et al[10] suggested that the close relationship of
hepatitis A virus with other enteroviruses known to cause
meningitis in humans might explain this phenomenon.
Furthermore, the frequently anicteric nature of hepatitis A
infection and the low index of suspicion might hinder the
identification of such cases, lowering the apparent incidence
of such disease.
Hepatitis E infection has also been reported in association
with a variety of neurological presentations such as
meningoencephalitis[11] and polyradiculoneuropathy[12,13].
Other associations include pseudotumour cerebri[14] and
acute transverse myelitis[15].
Pathogenetic mechanisms that have been postulated
include immune-medicated damage to axolemmal and
Schwann cell antigens, direct neuronal injury by viral
invasion of the central nervous system, and the presence of
neurotropic HEV quasispecies[16].
Kamar et al [16], described a case of central and peripheral
nervous system involvement in a patient with chronic
hepatitis E infection on immunosuppressant therapy. A
multi-center study by Kamar et al[17], found evidence of
neurologic disease in upto 5.5% of patients with acute or
chronic hepatitis E infection. Of the 126 patients involved
in this study, 55 were drawn from an organ-transplant unit.
Evidence such as this suggests that chronic hepatitis E
infection on a background of immunosuppression is a risk
factor for neurologic involvement.
Interestingly, our patient was immunocompetent, and both
hepatitis A and E viral infections were demonstrated by IgM
ELISA techniques, making chronic infection unlikely. One
possibility we did consider was whether acute synergistic
co-infection with two viruses might have resulted in overt
neurologic disease. However, if such synergism could indeed
occur, it would be much more likely to affect the liver first,
producing a more severe and virulent form of hepatitis than
that observed in our patient.
To conclude, our case represents a unique manifestation
of dual infection with hepatitis A and E viruses, in an
immunocompetent individual. Further studies are required
in patients with hepatitis A and E co-infection to determine
whether this presentation was an isolated event or not.
(ADEM)[2,3], Guillaine-Barre syndrome[4], acute myelitis [5,6]
Conflict of interest statement
We declare that we have no conflict of interest.
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