A Fatal Case of Enterovirus 71 Infection With a Single Nucleotide Variation in Domain V of the 5 Untranslated Region

To the Editors: Acute hepatitis A virus (HAV) infection is almost always an asymptomatic or mild illness with a benign outcome in infants and children, but the disease is often symptomatic in adults and fulminant forms can occur in them. We report the first case of fatal encephalitis in the preicteric stage of proven HAV infection in a female child. An 11-year-old Sudanese girl, in coma, was presented to our emergency department at Al-Jedaani Hospital, southern Jeddah, KSA. The girl had a high fever 2 days previously that responded to paracetamol. On the day of admission, she suddenly lost consciousness in the morning and was brought to our hospital. The child had no history of similar attacks or seizures. History of any disease and drug intake was negative, including preexisting liver disease and recent travel outside Jeddah. At the time of admission to our pediatric intensive care unit, the girl had been in coma for more than 4 hours. Her vital signs were normal. She was unresponsive to verbal stimulation (Galagow Coma Scale: 6/15). There was no pallor, jaundice, or cyanosis. There were no signs of meningeal irritation. Eye examination revealed bilateral normal fundi. Initial laboratory tests showed a hemoglobin concentration of 13.0 g/dL, total leukocyte count of 11,000/mm, with neutrophils 70%, and platelet count of 275,000/mm. The result of a blood film test was negative for malaria. C-reactive protein was positive at 11 mg/dL. Blood sugar, serum sodium, potassium, calcium, magnesium, creatinine, and arterial blood gases were normal. Urine analysis was also unremarkable. Initial liver function tests revealed a total serum bilirubin of 1.3 mg/dL, direct bilirubin of 0.2 mg/dL, alanine aminotransferase of 2280 U/L, mildly elevated alkaline phosphatase of 363 U/L, serum albumin of 3.6 g/dL, and prothrombin time of 14 seconds (control time: 12 s). Serum ammonia was normal (28 mol/L). The diagnosis was encephalitis and anicteric hepatitis. Cerebrospinal fluid (CSF) abnormal findings were protein of 80 mg/dL and white blood cell count of 400/mm with lymphocytes 65% and neutrophils 35%. Gramstained smear of the CSF revealed no microorganisms. Cultures for bacteria, fungi, and acid-fast bacilli were negative. The cranial computed tomographic findings were reported to be normal. After admission to pediatric intensive care unit, the girl remained in coma and developed fever (40°C) and tonic convulsions controlled by diazepam. By the end of the second day of admission, very mild icterus appeared. She developed frequent generalized tonic-clonic seizures unresponsive to diazepam, midazolam, and phenytoin, therefore general anesthesia with propofol was administered under mechanical ventilation, but convulsions and fever were not controlled, and the patient succumbed on the third day of admission. Follow-up of liver function tests mainly showed increased total and direct serum bilirubin to 4.2 and 3.5 mg/dL, respectively. Serologic tests for influenza, mumps, herpes simplex virus, coxsackie B3 virus, adenovirus, cytomegalovirus, epstein-barr virus, HAV, hepatitis E virus, hepatitis B virus, hepatitis C virus, and human immunodeficiency virus, and polymerase chain reaction specific for some infectious agents performed on blood and CSF specimens revealed that the only acute infection was HAV. This was proven by enzyme immunoassay for IgM antibody and polymerase chain reaction specific to HAV in both blood and CSF. Encephalitis during anicteric HAV infection has been previously reported rarely in adults but not in children. There is only one recent report of a case of a young boy from Tehran, Iran with HAV-associated meningoencephalitis in the icteric stage. However, all previously reported cases survived. In our case, the only clues to the diagnosis of HAV infection were abnormal initial and repeated liver function tests.