COMMENTARY
(Pages 154-55)
Hemolytic Uremic Syndrome
Along with a report of the first outbreak of hemolytic uremic
syndrome (HUS) caused by Shiga-like toxin (SLT) producing E. coli
in Australia (1), this issue of Emerging Infectious Diseases
presents three papers detailing the investigations of pediatric HUS
cases linked to Shiga toxin (ST) and SLT producing bacteria.
Goldwater and Bettelheim present a case of pediatric HUS associated
with SLT producing Escherichia coli (SLTEC) O48:H21 in South
Australia; this strain has not previously been recognized as an
SLTEC. Saeed et al. report on the increasingly common
identification of HUS in Saudi Arabia, its association with
multiple-antibiotic-resistant Shigella dysenteriae type 1, and the
inherent dangers of treating such patients with ampicillin and
nalidixic acid. Al-Qawari et al. report on the results of active
surveillance for dysentery and HUS in Saudi Arabia and discuss a
possibly elevated risk for HUS in patients with bloody diarrhea who
are hospitalized and treated with nalidixic acid during an outbreak
of S. dysenteriae type 1.
The three papers raise a number of important issues regarding HUS.
First, it is clear that a large number of SLT producing bacteria
have the potential to cause HUS, particularly among children.
Current research has focused on E. coli O157:H7, which since the
early 1980s has emerged as a major foodborne cause of bloody
diarrhea, hemorrhagic colitis, and HUS since the early 1980s (5-7).
However, the large outbreak of pediatric HUS in South Australia in
1995 caused by foodborne E. coli O111:HNM has demonstrated that
minor pathogens can emerge as major causes of HUS (1). Goldwater
and Bettelheim (5) and other researchers have identified a number
of E. coli serotypes isolated from patients with HUS (6,7).
A-Qawari et al. and Saeed et al. offer a timely reminder that S.
dysenteriae type 1, a pathogen with a human-only reservoir, is an
equally serious contender in HUS etiology and pathogenesis when
conditions facilitate the person-to-person transmission of
pathogens.
The second key issue raised by the latter two papers concerns
treatment of bloody diarrhea. Both discuss the potential for
antibiotic (ampicillin and nalidixic acid)-mediated HUS and
conclude that this issue should be carefully evaluated before
antibiotics are used to manage bloody diarrhea. Saeed et al. note
that the wide variety of antibiotics used to treat bloody diarrhea
in Saudi Arabia could be explained by the various prescription
practices of doctors recruited from different parts of the world.
Antibiotic resistance is a worrying component of the mechanisms of
emerging infectious diseases. Inappropriate antibiotic use is a key
factor in the development of resistance, and major efforts must be
directed towards educating physicians on effective prescribing
practices.
Central to all three papers is the need for surveillance of
organisms that cause bloody diarrhea, hemorrhagic colitis, and HUS,
as well as for knowledge of the local epidemiology of SLTECs, their
potential sources, and the optimal way to investigate and manage
outbreaks. Goldwater and Bettelheim discuss the characteristic
disappearance of E. coli from patients' stools after the
development of HUS and, therefore, the importance of early
detection in cases of bloody diarrhea. Laboratory testing of bloody
diarrheal specimens is clearly critical to understanding the
epidemiology of toxin-producing organisms that relate to the
development of HUS (8). However, testing can be difficult,
time-consuming and costly. Not all laboratories routinely test for
SLTECs or have the capacity to do so. In Australia, for example,
using polymerase chain reaction (PCR) technology to detect SLT
genes is expensive: a negative test result costs approximately
$A15, but if the results are positive, the cost rises to around
$A250 when the SLTEC is isolated and typed.
Human surveillance is essential to the early detection of outbreaks
and to the critical assessment of the impact on public health of
new approaches to food safety (2,8). We conservatively estimate
that the South Australian HUS outbreak has cost around $A20 million
in direct and indirect costs, with major impacts being felt by
industry. This must surely be considered when contemplating the
costs of surveillance. One approach may be to use PCR techniques on
all samples of bloody diarrhea in children under the age of 16
because if surveillance is to be effective, it must be specific
(9). Intermittent surveys, or the use of sentinel laboratories for
all cases of diarrhea (8) could be undertaken and mandatory
notification of HUS instituted.
Compulsory notification of Shigella infection is a requirement in
Australia, and including SLTECs on the list of notifiable diseases
is being considered. A national surveillance scheme for HUS was
established in 1994, although notification is not mandatory.
Without formal notification requirements, good reporting of HUS has
been associated with either clustering of cases or the fact that
few hospitals in a region have the capacity to manage these cases
(10).
Although more attention has been focused on E. coli O157:H7, S.
dysenteriae is likely the most common cause of HUS in children
worldwide and more attention needs to be given to this pathogen in
terms of surveillance and control. A strong and healthy public
health infrastructure is required to address the infectious disease
issues raised by HUS (11).
Mary Beers,* Scott Cameron 
*National Centre for Epidemiology and Population Health, and South
Australian Health Commission;  Communicable Disease Control Unit,
South Australian Health Commission, Adelaide, Australia
References:
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hemolytic uremic syndrome attributable to Escherichia coli
O111:NM South Australia, 1995. MMWR 1995;44:550-8.
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