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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ABSTRACT: Viral hepatitis ranks as the fifth cause of morbidity for infectious diseases in Cuba. Epidemics are observed frequently in the population, the hepatitis A virus being the main agent responsible for such epidemics. Previous reports also confirmed the circulation of the hepatitis E virus. From 1998 to 2003, 258 serum samples were collected by the Reference Laboratory on Viral Hepatitis during 33 outbreaks of acute viral hepatitis as well as from 39 sporadic clinical cases. Sera were tested for anti-HAV and anti-HEV IgM by EIA. Overall of the 33 outbreaks studied sera from 12 (36.4%) were positive for anti-HAV IgM only, from 7 (21.2%) were positive for anti-HEV IgM only, and from 14 (42.4%) were positive for antibodies to both viruses. Individually of the 258 sera collected, 137 (53.1%) were positives for anti-HAV IgM, 20 (7.8%) were positives for anti-HEV IgM, 33 (12.8%) were positives for both markers and 68 (26.4%) were negative to both. Of the clinical cases, 4 (10.3%) were positives for anti-HAV IgM, 13 (33.3%) were positives for anti-HEV IgM and 5 (12.8%) were positives for both markers. Seventeen (43.6%) sera were negatives for all viral hepatitis markers available (A–E). A high positivity for HEV was found in outbreaks tested with the kit produced by CIGB. In particular HEV seems to infect individuals of all ages. The results demonstrate the co-circulation of and co-infection with two enterically transmitted viruses; however a higher positivity was observed for anti-HAV than to anti-HEV (53.1% vs. 7.8%) in outbreaks. J. Med. Virol. 80:798–802, 2008. © 2008 Wiley-Liss, Inc.Journal of Medical Virology 03/2008; 80(5):798 - 802. · 2.37 Impact Factor
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ABSTRACT: Hepatitis virus A (HVA) infection is usually a benign infection, but it can lead to severe manifestations and neurological symptoms. We report the case of a 44-year-old man who was admitted for pyramidal tetraparesis, loss of proprioceptive sensitivity and cranial nerve involvement. He had developed concomitally jaundice and fatigue. Brain MRI and cerebrospinal fluid examination were normal. Blood tests revealed elevated serum transaminase and anti-hepatitis A virus (IgM and IgG) levels. Acute disseminated encephalomyelitis (ADEM) was diagnosed and the patient was treated with high dose intravenous then oral corticosteroid therapy. The clinical condition continued to deteriorate and the patient died at eight months. ADEM is exceptionally associated with HVA infection or after vaccination for hepatitis A. Other neurological complications, including either peripheral or central nervous system, are reported. The clinical presentation and the outcome of our patient are atypical.Revue Neurologique 09/2008; 164(10):852-4. · 0.51 Impact Factor
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ABSTRACT: We describe the case of a 30-month-old boy who developed acute disseminated encephalomyelitis (ADEM) after hepatitis A virus (HAV) infection and ultimately died. As far as we know, this is only the second case of HAV-associated ADEM to be reported in the literature. The child was brought to hospital with fever, lethargy and weakness of 2 days duration. He had developed jaundice, abdominal pain and malaise 2 weeks beforehand and these problems had resolved within 2 days. Neurological examination revealed lethargy, generalised weakness and positive Babinski's signs bilaterally. Cerebrospinal fluid examination showed mild lymphocytic pleocytosis, increased protein and elevated anti-HAV IgM and IgG titres. Serum HAV IgM and IgG titres were also elevated. Despite aggressive treatment with ceftriaxone, acyclovir and anti-oedema measures, he developed papilloedema and coma within 24 hours of admission. Magnetic resonance imaging of the brain revealed diffuse cerebral oedema and multifocal hyperintensities on T2-weighted images, with most lesions in the white matter of both cerebral hemispheres. The diagnosis of ADEM was established and high-dose steroids and intravenous immunoglobulin were added to the treatment regimen. However, his clinical condition continued to deteriorate and he died on the 20th day in hospital. This case shows that HAV infection can be linked with ADEM. Patients with HAV infection should be examined carefully for central nervous system symptoms during follow-up. Likewise, the possibility of HAV infection should be investigated in cases of ADEM.Annals of Tropical Paediatrics International Child Health 07/2004; 24(2):141-4. · 0.92 Impact Factor
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
＊, 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
ARTICLE INFO ABSTRACT
Received 10 November 2011
Received in revised form 15 January 2012
Accepted 15 March 2012
Available online 20 July 2012
*Corresponding author: Kushal Naha, Department of Medicine, Kasturba Medical
College, Manipal- 576 104, Karnataka, India
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, 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.
Kushal Naha et al./Asian Pacific Journal of Tropical Medicine (2012)587-588
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
Hepatitis A infection has been linked in sporadic reports
with a range of neurological manifestations including
meningoencephalitis, acute disseminated encephalomyelitis
and peripheral neuropathy. In children, hepatitis
A infection has been reported in association with
pseudotumour cerebri and abducens and palatal palsy.
Davoudi et al 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 and polyradiculoneuropathy[12,13].
Other associations include pseudotumour cerebri and
acute transverse myelitis.
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.
Kamar et al , 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, 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, acute myelitis [5,6]
Conflict of interest statement
We declare that we have no conflict of interest.
 Rodríguez Lay Lde L, Quintana A, Villalba MC, Lemos G,
Corredor MB, Moreno AG, et al. Dual infection with hepatitis A
and E viruses in outbreaks and in sporadic clinical cases: Cuba
1998-2003. J Med Virol 2008; 80(5): 798-802.
 El Moutawakil B, Bourezgui M, Rafai MA, Sibai M, Boulaajaj
FZ, Moutaouakil F, et al. Acute disseminated encephalomyelitis
associated with hepatitis A virus infection. Rev Neurol (Paris)
2008; 164(10): 852-854.
 Alehan FK, Kahveci S, Uslu Y, Yildirim T, Yilmaz B. Acute
disseminated encephalomyelitis associated with hepatitis A virus
infection. Ann Trop Paediatr 2004; 24(2): 141-144.
 Mihori A, Nakayama M, Ono S, Shimizu N. Ataxic form of
Guillain-Barré syndrome associated with acute hepatitis A-a case
report. Rinsho Shinkeigaku 1998; 38(3): 242-245.
 Ficko C, Imbert P, Mechaï F, Barruet R, Nicand E, Rapp C. Acute
myelitis related to hepatitis A after travel to Senegal. Med Trop
(Mars) 2010; 70(1): 7-8.
 Khemiri M, Ouederni M, Barsaoui S. A new case of acute
transverse myelitis following hepatitis A virus infection. Med Mal
Infect 2007; 37(4): 237-239.
 Islam S, McDonald JA. Sensory neuropathy in the prodromal
phase of hepatitis A and review of the literature. J Gastroenterol
Hepatol 2000; 15(7): 809-811.
 Thapa R, Ghosh A, Mukherjee S. Childhood hepatitis A virus
infection complicated by pseudotumor cerebri. South Med J 2009;
 Thapa R, Biswas B, Ghosh A, Mukherjee S. Unilateral palatal and
abducens palsy in childhood hepatitis A virus infection. J Child
Neurol 2009; 24(5): 628-629.
 Davoudi S, Soudbakhsh A, Emadikouchak H, Nikbakht G,
Modabbernia A. Meningoencephalitis associated with hepatitis A
infection: a case report and review of literature. Trop Doct 2010;
 Kejariwal D, Roy S, Sarkar N. Seizure associated with acute
hepatitis E. Neurology 2001;57:1935.
 Despierres LA, Kaphan E, Attarian S, Cohen-Bacrie S, Pelletier
J, Pouget J, et al. Neurologic disorders and hepatitis E. Emerg
Infect Dis 2011;17(8):1510-1512.
 Fong F, Illahi M. Neuralgic amyotrophy associated with hepatitis
E virus. Clin Neurol Neurosurg 2009; 111(2): 193-195.
 Thapa R, Mallick D, Biswas B. Pseudotumor cerebri in childhood
hepatitis E virus infection. Headache 2009; 49 (4):610-611.
 Mandal K, Chopra N. Acute transverse myelitis following hepatitis
E virus infection. Indian Pediatr 2006; 43(4): 365-366.
 Kamar N, Izopet J, Cintas P, Garrouste C, Uro-Coste E, Cointault
O, et al. Hepatitis E virus-induced neurological symptoms in a
kidney-transplant patient with chronic hepatitis. Am J Transplant
2010; 10(5): 1321-1324.
 Kamar N, Bendall RP, Peron JM, Cintas P, Prudhomme L, Mansuy
JM, et al. Hepatitis E virus and neurologic disorders. Emerg Infect
Dis 2011; 17(2):173-179.