Fulminant hepatitis A in Indigenous children in north Queensland
Jeffrey N Hanna, Tim H Warnock, Ross W Shepherd and Linda A Selvey
Since 1993, three Indigenous children in north Queensland have died
of fulminant hepatitis A. Even if the children had been able to undergo
liver transplantation, prolonged immunosuppressant therapy and
the likelihood of opportunistic infections would inevitably have
jeopardised any chance of long-term survival. As hepatitis A has
become a leading infectious cause of death in young Indigenous
children in north Queensland, hepatitis A vaccine has recently been
introduced into the vaccination schedule for these children.
MJA 2000; 172: 19-21
For editorial comment, see McCaughan & Torzillo
Clinical record 1 -
Clinical record 2 -
Clinical record 3 -
More articles on Aboriginal health
Fulminant hepatitis A is rare in children, and most recent reports
have been from developing countries.1-4 Occasional cases in
children from industrialised countries tend to be in those who have
recently travelled to hepatitis A endemic areas5,6 or who live in
conditions of considerable socioeconomic
We describe three cases of fulminant hepatitis A in Indigenous
children in north Queensland, all of whom died. This uncommon but
serious manifestation of a relatively common infection in
Indigenous children presents major difficulties in clinical
management,8 illustrating the
importance of preventive public health measures.
|Clinical record 1||
A 4.5-year-old Torres Strait Islander boy, who had previously been in
good health, presented to a local health centre in early 1993 with
anorexia, dark urine and jaundice of several days' duration.
Vomiting and irritability persisted for five days, and he was
evacuated to Thursday Island Hospital. Two days later, he had a
generalised seizure and became semi-comatose after an episode of
haematemesis, and was evacuated to Cairns Base Hospital.
On admission in Cairns, the boy was deeply jaundiced, with hepatic
fetor and moderate hepatomegaly. He did not respond to painful
stimuli, and was generally hypertonic with upgoing plantar
reflexes. He had raised serum bilirubin and liver enzyme levels,
markedly elevated serum ammonia level, hypoglycaemia and a bleeding
diathesis (see Box). He was positive for hepatitis A IgM, confirming
acute hepatitis A; subsequent serological tests were negative for
hepatitis B and C, cytomegalovirus (CMV) and herpes simplex virus
The boy was stabilised, placed on ventilator support and transferred
the next day to the Royal Children's Hospital in Brisbane for
consideration of liver transplantation. However, on arrival in
Brisbane, he had fixed, dilated pupils, and urgent computed
tomography showed gross cerebral oedema. Despite intensive
treatment, his condition deteriorated, and he died the next day, nine
days after initial presentation.
Postmortem examination showed massive hepatic necrosis and diffuse
hypoxic ischaemic brain injury, secondary to cerebral oedema and
raised intracranial pressure.
|Clinical record 2||
A 4.5-year-old Aboriginal girl was admitted to a community hospital
near Townsville in late 1997 with fever, lethargy, dark urine and
jaundice of uncertain duration. Apart from a persistent tinea
capitis infection, she had been in reasonably good health. Four
months before the current illness, she had been treated with a
four-week course of ketoconazole, and results of liver function
tests were normal at that time.
On admission, she had raised serum bilirubin and liver enzyme levels
(Box). Serological tests confirmed acute hepatitis A;
subsequent tests were negative for hepatitis B and C, CMV, HSV and
Epstein-Barr virus infection. Four days after her admission, the
girl's family took her from the hospital, and on her return the next day
she was delirious. She was transferred to Townsville General
On admission in Townsville, she was deeply jaundiced and irritable,
with a depressed level of consciousness and moderate hepatomegaly.
Peripheral reflexes were brisk, with up-going plantar reflexes and
bilateral ankle clonus. Her serum bilirubin level had risen further
(Box), she was hypoglycaemic, had a bleeding diathesis, and soon
became hypokalaemic (serum potassium level, 2.7 mmol/L [RR, 3.5-4.5
mmol/L]). Several hours after admission, she had an episode of
profound hypotension (systolic pressure, 50 mmHg) after aspiration
of a large volume of bloodstained fluid from the nasogastric tube.
She was transferred the next day to the Royal Children's Hospital in
Brisbane for consideration of liver transplantation. On arrival in
Brisbane, her serum ammonia and sodium levels were both markedly
elevated (ammonia, 158 µmol/L; sodium, 151 mmol/L [RR,
133-143 mmol/L]). Computed tomography showed cerebral oedema with a
possible ischaemic lesion in the right cerebral hemisphere. She was
listed for urgent liver transplantation pending a suitable donor,
but the next day developed signs of raised intracranial pressure
which did not respond to medical management. She died eight days after
|Clinical record 3||
A 2.5-year-old Aboriginal girl, who had previously been in good
health, presented to a health centre in a Cape York community in
September 1998 with malaise and jaundice of one day's duration. She
was reviewed the next day by the visiting Royal Flying Doctor Service;
a clinical diagnosis of acute hepatitis was made, but, because she did
not appear particularly unwell, no specific treatment was
requested. Liver function tests on that day (Day 2) showed her serum
concentrations of bilirubin, AST and ALT were raised (Box).
Serological testing confirmed acute hepatitis A, and tests for
hepatitis B and C were negative.
The girl was reviewed two days later by health centre staff. She
reportedly had stopped eating and appeared lethargic, although she
responded appropriately to voices and other stimuli. When seen the
next morning, she had deteriorated markedly, no longer responded to
her environment and was obtunded and dehydrated, with grunting
respirations. She was evacuated urgently to Cairns Base Hospital.
On admission in Cairns she was deeply jaundiced, with hepatic fetor
and mild hepatomegaly. She was semi-comatose, had brisk symmetrical
reflexes and upgoing plantar reflexes. Her serum ammonia level was
markedly raised and she had a bleeding diathesis (Box). Urgent
transfer to Brisbane was arranged, but she deteriorated nine hours
after admission with extensor posturing and diminished respiratory
effort; her limbs subsequently became flaccid and areflexic. She
died several hours later, five days after initial presentation.
All three of the reported children were critically ill with fulminant
liver failure and grade III hepatic encephalopathy9 when referred to
specialist services in Cairns or Townsville. Mortality rates in
fulminant hepatitis approach 70% in children,8 with death
usually occurring within 8-10 days. Youth and severity of hepatic
encephalopathy are both strong predictors of poor
outcome;10 the main cause of death is
Liver transplantation is the only option for children with fulminant
hepatitis A and advanced stages of encephalopathy who are considered
unlikely to survive with medical supportive therapy
alone.6,8-10 Published criteria
for transplantation include either PT > 100 s or any three of the
following: PT > 50 s, age < 10 years or > 40 years, jaundice
for > 7 days before onset of encephalopathy, or serum bilirubin
> 300 µmol/L.11 However, in practice, the
availability of a suitable donor organ may be the critical issue, and
therefore most transplant centres list patients as soon as
transplantation is considered, and make a final decision if and when a
donor organ becomes available.8 Two of the children
(Patients 1 and 2) clearly met the above criteria and were listed for
urgent transplantation on arrival in Brisbane, but it soon became
apparent that irreversible brain damage had occurred. However, even
if they had received a successful liver transplant, the difficulties
of monitoring prolonged immunosuppressant therapy and the
likelihood of opportunistic infections in their home communities
would have inevitably jeopardised any chance of long-term survival.
Hepatitis A has been the most frequent infectious cause of death in
preschool-aged Indigenous children in north Queensland since 1993
(excluding neonatal deaths and pneumococcal infections, for which
data are incomplete) (J Hanna, unpublished data). Two deaths
resulted from the "standard" vaccine-preventable diseases
(measles and Haemophilus influenzae type b infection), and
one from meningococcal infection. Over the same period, no
non-Indigenous children died of hepatitis A in north Queensland. We
can only speculate that "host factors", as well as the quantity of
viral inoculum,6 may determine why some
Indigenous children develop fulminant hepatitis A.
The notification rates of hepatitis A in children under five years of
age in north Queensland in 1996-1997 were 264 and 10 per 100 000 in
Indigenous and non-Indigenous children, respectively.12 About 25% of
notified cases of hepatitis A in Indigenous people in north
Queensland occur in children under five years of age,12 indicating
considerable circulation of the hepatitis A virus among these young
children. However, nearly half the notified cases in Indigenous
people in north Queensland occur in children aged 5-14
years,12 indicating that many
Indigenous primary school-aged children are susceptible to the
infection. Very few notifications are in Indigenous adults over 30
years of age.
Because hepatitis A is common in Indigenous children in north
Queensland, and because of the demonstrated unsatisfactory outcome
in those few children who develop fulminant liver failure, the
emphasis must be on preventing infection.
Hepatitis A virus is readily transmitted in environments with
inadequate sanitation and water supply, suboptimal hygiene and
overcrowding.13 The current status of
housing and environmental health infrastructure throughout
Indigenous Australia has recently been detailed elsewhere, and
others have described some of the health consequences of these
circumstances.14,15 Despite considerable
recent improvements in provision of adequate housing and sanitation
infrastructure in several Indigenous communities in north
Queensland, many communities still have unresolved problems of
overcrowding, water supply and waste disposal.16 Some
communities continue to experience environmental contamination by
raw sewage during wet season floods, and several Torres Strait Island
communities experience severe water shortages in the dry
Some of these problems are likely to persist for the foreseeable
future. Paradoxically, as environmental circumstances improve,
the age of reported patients will likely shift upwards, and the
"visibility" of hepatitis A -- and public health concern -- will
increase.13 Indigenous communities
in North America have experienced cyclical outbreaks of hepatitis A
every 5-10 years for many years,18 a pattern that may become
more obvious in Indigenous Australian communities.
Inactivated vaccines with proven effectiveness in preventing
hepatitis A in children19,20 have recently become
available in Australia. These vaccines have also been shown to
interrupt transmission in "closed" communities prone to recurrent
outbreaks,21,22 leading to the
recommendation of routine hepatitis A vaccination for Indigenous
children in North America.18
An inactivated hepatitis A vaccine has been offered to Indigenous
children in north Queensland since early 1999. Two doses six months
apart have been recommended, integrated as far as possible into the
standard vaccination schedule, with the first dose at 18 months of age
and the second at 24 months, necessitating only one "extra" visit to a
vaccination service. Current resources allow for catch-up
hepatitis A vaccination up to the sixth birthday; about 5500
Indigenous children aged 2-5 years live in north Queensland.
Young children play a particularly important role in maintaining
transmission of hepatitis A virus to older susceptible individuals
during community-wide outbreaks,24 because of their lack of
bowel control and attention to hygiene, and need for adult
supervision of their toileting needs. Therefore, vaccination of
preschool-aged Indigenous children provides a means not only to
prevent further cases of fulminant hepatitis A in Indigenous
Australian children, but also to reduce the extent of future
outbreaks in their communities. A particular challenge will be to
ensure that Indigenous children in rural towns and urban settings
gain access to the vaccine.25
We wish to thank the families of the three children for allowing us to
describe their children's final illness.
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(Received 6 Apr, accepted 24 Aug, 1999)
Queensland Health, Cairns, QLD.
Jeffrey N Hanna, MPH, FAFPHM, Public Health Physician,
Tropical Public Health Unit;
Tim H Warnock, FRACP,
Paediatrician, Cairns Base Hospital.
Department of Gastroenterology and Hepatology, Royal Children's
Hospital, Brisbane, QLD.
Ross W Shepherd, MD, FRACP, Director.
Communicable Diseases Unit, Queensland Health, Brisbane, QLD.
Linda A Selvey, PhD, FAFPHM, Manager.
Reprints will not be available from the authors.
Correspondence: Dr J
N Hanna, Tropical Public Health Unit, Queensland Health, PO Box 1103,
Cairns, QLD 4870.
Results of investigations of three Indigenous children with fulminant hepatitis A|
|Reference||Patient 2||Patient 3|
|Test||range||Patient 1||On admission||Day 5||Day 2||Day 5|
|Serum bilirubin level (µmol/L)||<20||389||166||269||225||202|
|Aspartate aminotransferase level (U/L)||10-60||1601||6785||1378||5367||2279|
|Alanine aminotransferase level (U/L)||<40||1750||2690||1873||2285||1352|
|Blood glucose level (mmol/L)||3.5-6.0||1.7||ND||1.9||ND||3.2|
|Prothrombin time (s)||10-15||>180||ND||147||ND||84|
|Activated partial thromboplastin time (s)||23-37||135||ND||107||ND||65|
|Serum ammonia level (µmol/L)||10-35||416||ND||ND||ND||205|
ND = not done