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1www.eurosurveillance.org
R
Household transmission of haemolytic uraemic
syndrome associated with Escherichia coli O104:H4 in
the Netherlands, May 2011
E J Kuijper (e.j.kuijper@lumc.nl)1, D Soonawala2, C Vermont3, J T van Dissel4
1. Department Medical Microbiology, Centre for Infectious Diseases, Leiden University Medical Centre, Leiden, the Netherlands
2. Department of Nefrolog y, Leiden University Medical Centre, Leiden, the Netherlands
3. Department of Paediatrics, Leiden University Medical Centre, Leiden, the Netherlands
4. Department of Infectious Disease, Centre for Infectious Diseases, Leiden University Medical Centre, Leiden, the Netherlands
Citation style for this article:
Kuijper EJ, Soonaw ala D, Vermont C, va n Dissel JT. Household transmission of haem olytic uraemic syndrome associated with E scherichia coli O104:H4 in the
Nether lands, May 2011.
Euro Sur veill. 2011;16(25 ):pii=19897. Available onlin e: http://www.eurosurveillance.org/ ViewArt icle.aspx?Ar ticleId=198 97
Article published on 23 June 2011
Following the outbreak of haemolytic uraemic syn-
drome (HUS) and haemorrhagic colitis in Germany,
two patients returning from a stay in Germany devel-
oped HUS due to Escherichia coli O104:H4 in the
Netherlands. The index case developed symptoms
eight days, and her child 15 days after their return. It
is very likely that transmission resulted from second-
ary spread from mother to child. Recommendations
should be made to prevent secondary transmission
within households.
Introduction
Since early May 2011 one of the largest ever reported
outbreaks of haemolytic uraemic syndrome (HUS) and
bloody diarrhoea caused by Shiga toxin/verotoxin-
producing Escherichia coli (STEC/VTEC), also referred
to as enterohaemorrhagic E. coli (EHEC) has affected
Germany [1]. The outbreak strain was identified as
an enteroaggregative Shiga toxin-producing E. coli
O104: H4 (EAggEC) [2]. Initial findings suggested raw
vegetables and salads as vehicle of infections and
recommendations were made to abstain from these
products. Epidemiological investigations implicated
an organic sprout farm in Lower Saxony near Hamburg
as the potential source of the outbreak [3]. On 10 June
2011, German public health and food safety authori-
ties issued a joint statement recommending people
to abstain from consuming sprouts. A decrease in the
number of new cases was seen after 6 June [4].
We describe here two cases of HUS and hemorrhagic
colitis that occurred in the Netherlands and were asso-
ciated with the outbreak in Germany.
Case descriptions
Patient A
On 24 May, a woman in her 30s was admitted to a hospi-
tal in the Netherlands with bloody diarrhoea and abdom-
inal pain of two days. Common bacterial gastroenteritis
was considered and no antibiotic treatment was initi-
ated. Four days after admission, blood examination
revealed severe HUS. The patient was transferred to the
Leiden University Medical Centre (LUMC) for haemodi-
alysis which eventually proved not to be necessary.
A tentative diagnosis of HUS due to Stx1-negative,
Stx-2 positive, extended spectrum beta-lactamase
(ESBL)-producing E. coli was confirmed by culture on
sorbitol MacConkey agar of a stool sample collected
two days after admission to the first hospital. Further
identification of E. coli serotype O104 was performed
at the Dutch National Institute for Public Health and the
Environment (RIVM). A real-time PCR for Stx2 directly
in stool sample was also positive [5]. Stool samples
on admission to LUMC were already negative in culture
and real-time PCR. Since 30 May 2011, the patient has
gradually been recovering from HUS.
Patient A had travelled to Northern Germany for two
days in May 2011, accompanied by six relatives, among
them her 10 month-old child.
Patient B
The 10-month-old child of Patient A was examined first
on 29 May 2011, one day after transfer of the mother
to the LUMC. At the time, the child had mild diarrhoea
free of blood, and blood examination did not reveal any
abnormality. A stool sample was collected and tested
positive for Stx2 in the real-time PCR. Culture revealed
growth of ESBL-positive E. coli O104. On 30 May, the
child developed fever and blood abnormalities compat-
ible with HUS, and was admitted to hospital. The next
day, it developed neurological symptoms, i.e. seizures,
and was transferred to a specialised child dialysis cen-
tre, where experimental treatment with eculizumab
was started. The patient received prolonged mechani-
cal ventilation and inotropic therapy. Three weeks after
transfer, the patient is still on dialysis and the neuro-
logical outcome is unsure.
2www.eurosurveillance.org
Family members
Of the other five relatives of Patients A and B who had
also travelled to Northern Germany, one developed
mild diarrhoea 16 days after their return, but micro-
biological examinations were not performed since the
diarrhoea resolved one day later and no HUS devel-
oped. The remaining relatives did not develop any
symptoms and were not investigated for the presence
of E. coli O104.
Microbiological and public
health implications
HUS is a rare disease in the Netherlands, with approxi-
mately 20 patients per year [6]. During the outbreak
in Germany, 854 cases of HUS and 2,848 non-HUS
STEC/VTEC cases have been reported as of 22 June,
of which 4.6% and 2.2%, respectively, were found
in other Member States of the European Union [7]. In
the Netherlands, four HUS (including Patients A and
B described here) and five non-HUS laboratory-con-
firmed STEC/VTEC cases were detected. All acquired
the infection during a recent visit to Germany.
Microbiological examination of stool samples from
Patient A gave negative results in the real-time PCR
and culture at the time of transfer to another hospital
when HUS had fully developed, six days after disease
onset, indicating the need to apply diagnostic tests
early in the disease. Similarly, Patient B had positive
faeces tests and excreted the organism before haemor-
rhagic colitis and HUS developed.
We hypothesise that Patient B probably acquired HUS
by secondary transmission within the household,
because the child developed illness only 15 days after
return form Northern Germany. The child had spent
much time with her mother during her stay at the
first hospital, when the mother developed diarrhoea.
Before admission of the child to LUMC, the mother had
not been advised to take any specific hygienic meas-
ures. The child was not breastfed at the time. The age
of the child makes it unlikely that it had eaten a food
product such as sprouts.
Recently, a group of investigators reported that the
strain causing the outbreak in Germany is in fact not a
typical virulent Shiga toxin-producing Escherichia coli
strain, but instead is a more rare, hybrid pathotype
that harbours the phage encoded the Shiga toxin gene
in an EAggEC background [2]. These findings are rele-
vant for understanding the epidemiology since EAggEC
is a common pathogen causing diarrhoea in travellers
and persistent diarrhoea in infants and young children
living in countries with poor sanitation. In contrast to
STEC/VTEC strains, which that have an animal reser-
voir, mostly ruminants, EAggEC strains probably have
a human reservoir only.
Secondary transmission frequently occurs in out-
breaks caused by classical EHEC O157. A review of 90
confirmed outbreaks in the United Kingdom, Ireland,
Scandinavia, Canada, the United States and Japan
revealed that approximately 20% of all outbreak cases
were the result of secondary spread [8]. Interestingly,
the spread was significantly influenced by age and
modes of transmission. A lower median age of the
index patients was associated with a higher rate of
secondary cases and household contacts aged one
to four years were most likely to become infected.
Immediate separation of a paediatric patient from its
siblings when there is a clinical suspicion of STEC/
VTEC O157 infection has been suggested as an impor-
tant measure in the prevention of secondary cases [9].
Isolation of all symptomatic primary patients immedi-
ately after they receive a microbiological diagnosis of
STEC/VTEC O157 infection could potentially decrease
the number of secondary household cases by 50% [9].
In this family however, the primary case patient was
an adult. Since young children usually have extensive
close contacts with their parents; separation of young
children from a parent with a suspected STEC/VTEC or
E. coli O104 infection should be considered in order to
prevent secondary transmission to the child.
Acknowledgements:
We thank dr. E. Franz (Laborator y for Zoonoses and
Environmental Microbiolog y, Centre for Infectious Disease
Control Netherlands, National Institute for Public Health and
the Environment), dr. A Timen (Centre for Infectious Disease
Control, the Netherlands), dr. E. Wessels (Leiden University
Medical Centre) and dr. P. Voorn (St. Antonius Hospital,
Nieuwegein, the Netherlands) for their contribution for this
short report.
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