Content uploaded by Ran Li
Author content
All content in this area was uploaded by Ran Li on Sep 15, 2018
Content may be subject to copyright.
Review
Australian carybdeid jellyfish causing “Irukandji syndrome”
James Tibballs
a
,
b
,
*
, Ran Li
b
,
c
, Heath A. Tibballs
d
, Lisa-Ann Gershwin
e
, Ken D. Winkel
b
a
Intensive Care Unit, Royal Children’s Hospital, Flemington Road, Parkville 3052, Australia
b
Australian Venom Research Unit, Department of Pharmacology, The University of Melbourne, Australia
c
Cardiovascular Therapeutics Unit, Department of Pharmacology, The University of Melbourne, Australia
d
The University of Melbourne, Australia
e
Curator of Natural Sciences, Queen Victoria Museum and Art Gallery, Launceston, Tasmania, Australia
article info
Article history:
Received 19 April 2011
Received in revised form 18 January 2012
Accepted 31 January 2012
Available online 14 February 2012
Keywords:
Jellyfish
Irukandji
Carybdeids
Envenomation
Envenoming
Catecholamine
abstract
The Australian carybdeid jellyfish associated with Irukandji syndrome is Carukia barnesi,
(Barnes’jellyfish). Other Australian carybdeid jellyfish that may be associated with the
syndrome include Carukia shinju,Carybdea xaymacana,Malo maxima,Malo kingi,Alatina
mordens,Gerongia rifkinae,andMorbakka fenneri (“Morbakka”). These small jellyfish are
difficult to capture and identify. They are located offshore of the coasts of Australian
states including Queensland, The Northern Territory, Western Australia and South
Australia. The syndromic illness, resulting from a characteristic relatively minor sting,
develops after about 30 minutes and consists of severe muscle pains especially of the
lower back, muscle cramps, vomiting, sweating, agitation, vasoconstriction, prostration,
hypertension and in cases of severe envenomation, acute heart failure. The mechanisms
of actions of their toxins are obscure but they appear to include modulation of neuronal
sodium channels leading to massive release of endogenous catecholamines (C. barnesi,
A. mordens and M. maxima) and thereby to possible stress-induced cardiomyopathy. In
addition, pore formation may occur in myocardial cellular membranes (C. xaymacana). In
human cases of severe envenomation, systemic hypertension and myocardial dysfunc-
tion are associated with membrane leakage of troponin. Clinical management includes
parenteral analgesia, antihypertensive therapy, oxygen and mechanical ventilation. No
effective first-aid is known. Large knowledge gaps exist in biology of the jellyfish, their
distribution, their toxins and mode of actions and in treatment of the Irukandji
syndrome.
Ó2012 Elsevier Ltd. All rights reserved.
1. Introduction
Carybdeids (Order Carybdeidae, Class Cubozoa) are
“box”jellyfish with a cubic medusal bell and a single
tentacle arising from each of four corners. These jellyfish
are small and difficult to see, capture and to identify. These
factors have contributed to tardy recognition and poor
understanding of an unusual serious illness, the “Irukandji
syndrome”, caused by the stings of some species (Table 1).
This review presents the current state of knowledge of the
species involved, their venoms and mechanisms of actions,
the illness resulting from envenomation and its manage-
ment, and deficiencies in knowledge.
Although first recognised in Australia, Irukandji
syndrome has been reported from Papua New Guinea,
Hawaii, Fiji, Japan and China (Cleland and Southcott, 1965;
Williamson et al., 1996; Yoshimoto and Yanagihara, 2002).
An ‘Irukandji-like’syndrome has been observed or suspected
in victims of stings from Florida (Grady and Burnett, 2003),
the Gulf Sea near Qatar (Salam et al., 2003), Thailand (de
Pender et al., 2006) and the Caribbean (Pommier et al., 2005).
*Corresponding author. Intensive Care Unit, Royal Children’s Hospital,
Flemington Road, Parkville 3052, Australia. Tel.: þ61 3 9345 5221;
fax: þ61 3 9345 6239.
E-mail address: james.tibballs@rch.org.au (J. Tibballs).
Contents lists available at SciVerse ScienceDirect
Toxicon
journal homepage: www.elsevier.com/locate/toxicon
0041-0101/$ –see front matter Ó2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.toxicon.2012.01.006
Toxicon 59 (2012) 617–625
Carybdeids of medical importance in Australia include
Carukia barnesi,(Barnes’jellyfish), Carukia shinju,C. xay-
macana,Malo maxima,Malo kingi,A. mordens,Gerongia
rifkinae,andMorbakka fenneri (“Morbakka”). Detailed
information on the taxonomy of carybdeids and dis-
tinguishing morphological features of different species
may be found in Bentlage et al. (2010), Gershwin (2005a,
2005b, 2007, 2008), Gershwin and Alderslade (2005)
and in Williamson et al. (1996).
2. Carukia barnesi (“Barnes’jellyfish”)
This creature is minute compared with other dangerous
jellyfish (Fig. 1). Its squarish bell is barely 2 cm wide and
2.5 cm long and the four tentacles vary in length from a few
to 35 cm (Williamson et al., 1996). Clumps of nematocysts
appear as tiny red dots over the body and as tightly packed
‘collars’on the tentacles. Very little is known about the
habits of C. barnesi. It appears in shallow waters in summer
months and approaches the shore when seas are rough.
From the 1920s, bathers near Cairns in north Queens-
land reported an unusual type of marine sting, subse-
quently termed the “Irukandji syndrome”.Flecker (1952)
named the illness after an Aboriginal tribe that formerly
inhabited the area north of Cairns, where it is commonest.
The sting was only moderately painful and immediate
effects were not serious, but an hour or so later a severe
systemic illness usually occurred. The jellyfish responsible
was not captured until 1961 after several cases of Irukandji
syndrome had occurred (Barnes, 1964). It was named by
Southcott (1956) who constructed the generic name ‘Car-
ukia’from ‘Carybdea’and ‘Irukandji’and chose the species
name to commemorate Barnes.
Although appropriate to retain the phrase “Irukandji
syndrome”as a descriptor of the illness caused by
C. barnesi, it is confusing to retain “The Irukandji”as the
common name for C. barnesi since numerous other jellyfish
are now known or suspected to cause the same or a similar
syndrome. “Barnes’jellyfish”is a preferable common name
for C. barnesi (Little and Seymour, 2003; Little et al., 2003).
Originally, the range of this species was considered vast.
Barnes (1966) and Williamson et al. (1996) assumed that
its range corresponded to the occurrence of Irukandji
syndrome from Broome in Western Australia to east of
Childers near Fraser Island in Queensland. However, this is
probably false because other species, in addition to C. bar-
nesi, also cause the syndrome and inhabit these regions.
The range of C. barnesi is probably confined to Queensland
waters as far south as Mackay (Fenner, 2004).
2.1. Venom
The venom is proteinaceous. It contains a potent
neuronal sodium channel modulator as indicated by
in vitro experiments in which whole animal extracts
causing systemic and pulmonary hypertension and
increases in cardiac output were blocked by tetrodotoxin
(Winkel et al., 2005). Venom derived from tentacle
extracts (Tibballs et al., 2000; Winkel et al., 2005) and from
nematocysts (Ramasamy et al., 2005) induced hyperten-
sion in experimental anaesthetised animals. This hyper-
adrenergic state explains some of the clinical features of
Irukandji syndrome.
3. Human envenomation, the “Irukandji syndrome”
3.1. Local effects
The offending jellyfish is not usually seen but the victim
feels the pain of a sting within a few seconds of contact. The
Table 1
Timeline of advances in Irukandji syndrome research.
Date Event
1945 Description of ‘type A’(non Chironex fleckeri) jellyfish stings (Southcott, 1945)
1952 Term “Irukandji syndrome”used as a descriptor (Flecker, 1952)
1956 Small carybdeid jellyfish discovered and described (Southcott, 1956)
1961 Small carybdeid jellyfish considered the cause of Irukandji syndrome (Barnes, 1964)
1967 Carybdeid jellyfish causing Irukandji syndrome described and classified as Carukia barnesi (Southcott, 1967)
1986 Irukandji syndrome with severe hypertension hypothesised due to sympathetic over-stimulation (Fenner, 1986a)
1987 Acute pulmonary oedema recognised as a component of Irukandji syndrome (Herceg, 1987)
2000 C. barnesi extracts cause massive release of catecholamines in experimental animals (Tibballs et al., 2000)
2001 Life-threatening cardiac failure occurs in a case of Irukandji syndrome (Little et al., 2001).
2002 Two fatalities attributed to Irukandji syndrome in Queensland, both due to intracerebral haemorrhage secondary to
hypertension (Fenner & Hadok, 2002; Huynh et al., 2003)
2003 Huynh et al. (2003) identify nematocyst scrapings from one of the fatalities as not belonging to Carukia barnesi –the first
non-anecdotal evidence that other species may cause Irukandji syndrome. It was later re-argued by Pereira et al. (2010)
that the nematocysts originated from hitherto unobserved mature Carukia barnesi.
Irukandji syndrome recognised in USA (Grady & Burnett, 2003)
2004 Intravenous magnesium used effectively to treat Irukandji syndrome (Corkeron et al., 2004). Irukandji syndrome reported
from Broome (Macrokanis et al., 2004)
2005 New species of carybdeids identified: Malo maxima, Carukia shinju, Alatina mordens and Gerongia rifkinae (Gershwin, 2005a;
Gershwin 2005b; Gershwin & Alderslade, 2005 )
2005 Pharmacological analysis of Carukia barnesi venom extracts confirming release of catecholamines (Winkel et al., 2005;
Ramasamay et al., 2005) and modulation of neural sodium channel (Winkel et al., 2005).
2006 Irukandji syndrome recognised in South East Asia (de Pender et al., 2006)
2007 Identification of another species of carybdeid: Malo kingi (Gershwin, 2007)
2008 Re-classification of genus of carybdeid: Morbakka fenneri (Gershwin, 2008). Catecholamine release by Alatina nr mordens
(Winter et al., 2008).
J. Tibballs et al. / Toxicon 59 (2012) 617–625618
pain is not severe and tends to wane over the next thirty
minutes but it is often sufficient to force the victim to leave
the water. There is no skin banding or puncture mark,
merely an oval area of barely perceptible erythema
measuring 5 cm by 7 cm, which is much larger than the
area of contact with the bell (Barnes, 1964). Within 20 min
of the sting, irregularly spaced papules up to 2 mm in
diameter develop and then fade but the erythema may last
several days (Fenner and Carney, 1999). Sweating is far
more profuse around the area of the sting than elsewhere.
3.2. Systemic effects
The initial phase of the syndrome commences within
minutes and culminates in severe muscle pains especially
of the lower back, muscle cramps, vomiting, sweating,
agitation, vasoconstriction, prostration and hypertension.
Although an “Irukandji-like”or a “mild Irukandji
syndrome”may exist, there is little to differentiate or
subdivide the syndrome apart from severity and effects
recorded from various eras and recorded from various
locations around Australia.
3.2.1. Irukandji syndrome in Queensland
Although the syndrome was named by Flecker in
1952, it had been recognised as a distinctive marine enve-
nomation as early as 1945 (Flecker) and had been previ-
ously referred to as “Type A stingings”(Southcott, 1952).
Barnes (1964) detailed the illness in victims presenting
to Cairns Hospital. From 5 min to as late as two hours after
the sting, marked general symptoms developed. Nausea,
vomiting, profuse sweating and agitation occurred almost
invariably. Abdominal pain was often associated with
spasm of the muscles of the abdominal wall and cramps in
limb muscles. Sometimes cutaneous areas of numbness
and tingling occurred. Pain could occur around the larger
joints, especially shoulder and hip. As a general rule the
victim’s temperature remained normal. Full recovery
occurred after one or two days of nausea, pain and
prostration.
In a study of 62 cases presenting to Cairns Hospital
during 1996 (Mulcahy and Little, 1997; Little and Mulcahy,
1998), the symptoms and signs were abdominal cramps
(40%), hypertension (50%), back pain (39%), nausea and
vomiting (39%), limb cramps (34%), chest tightness (26%)
and marked distress (24%).
In another study of 116 patients presenting to Cairns
Hospital with Irukandji syndrome over a 12-month period
2001–2002 (Huynh et al., 2003), severe pain and hyper-
tension were common. Of importance was that of 40
victims with the syndrome who had skin scrapings, 39 had
nematocysts characteristic of the cnidome of C. barnesi
[the largest series of definite C. barnesi cases to date]
while the remaining case had nematocysts of uncertain
identity. Although no victim had pulmonary oedema, many
had raised troponin levels ranging from 1 to 34 ug/L
Fig. 1. Carybdeid jellyfish. Left to right. Top panel: undescribed species from Ningaloo Reef (photo Pat Baker), Malo kingi,Morbakka fenneri. Middle panel: Carukia
barnesi,C. shinju,Malo maxima (photo Mark Alexander, Paspaley Pearling Company), Gerongia rifkinae. Bottom panel: unnamed species of Carukia,Alatina
mordens, undescribed species from New South Wales.
J. Tibballs et al. / Toxicon 59 (2012) 617–625 619
(normal <0.4). Some victims also had ECG abnormalities
and echocardiographic abnormalites ranging from mild
impairment of systolic function to global myocardial
dysfunction which in two victims persisted for 3 and 6
months. One of the victims in this series, a 44-year-old man
who had been stung at Opal Reef (Great Barrier Reef some
1300 km north of Port Douglas) developed severe hyper-
tension (230/90 mmHg), a high troponin level (34 ug/L)
and sustained an intracranial haemorrhage from which he
died (Huynh et al., 2003). Another fatality attributed to
Irukandji syndrome occurred in the Queensland Whit-
sunday Islands but no nematocysts were recovered from
the victim’s skin to confirm the cause of death and
assist identification of a jellyfish (Fenner and Hadok, 2002;
2003), notwithstanding the inherent difficulties with that
technique. Although the victim experienced a sting and
subsequent symptoms consistent with Irukandji syndrome,
the diagnosis was questioned (Dawson, 2003; Bailey,
2003).
Two subsequent attempts have been made to identify
the jellyfish which caused the death of the man stung at
Opal Reef (Huynh et al., 2003) but both were based only on
the nematocysts retrieved from skin scrapings, and illus-
trate the possible obfuscation which may follow in this
circumstance. The cnidome was originally unidentifiable
(Huynh et al., 2003) but Gershwin (2007) later attributed it,
tentatively, to a newly recognised species of carybdeid,
M. kingi. However, the cnidome was then subsequently re-
examined and postulated to be from C. barnesi on the
basis that the nematocysts were characteristic of a mature
C. barnesi which hitherto had never been previously
observed (Pereira et al., 2010). Considering that nemato-
cysts obtained from skin scrapings are subject to distortion
during their discharge, collection and processing (Nickson
et al., 2009), it is reasonable to conclude that the true
taxonomic identity of the jellyfish remains in doubt.
3.2.2. Irukandji syndrome in Western Australia
In a series of 88 patients with Irukandji syndrome
reporting to Broome Hospital after stings sustained mainly
at Cable Beach between 2001 and 2003, 80% of victims had
cutaneous signs of a sting, 50% were hypertensive and 90%
required opiate analgesia (Macrokanis et al., 2004). Of two
victims who developed pulmonary oedema, one required
mechanical ventilation (Little et al., 2003; Macrokanis et al.,
2004). Compared to patients presenting to Cairns Hospital
in Queensland (Little and Mulcahy, 1998), this study
recorded a similar incidence of hypertension (around 50%
of patients) and pulmonary oedema (around 3%) but
a higher rate of hospital admission (54% cf 17%). Until a high
quality, long-term prospective study of clinical studies
using similar objective outcome measures has been con-
ducted, it is difficult to differentiate the syndromes
observed in Western Australian and north Queensland.
3.2.3. Irukandji syndrome in the northern territory
In a prospective study of victims with jellyfish stings
presenting to the Royal Darwin Hospital from 1999 to 2000
(O’Reilly et al., 2001), 4 of 40 patients had Irukandji
syndrome but nematocysts could not be identified from
any sting site. The most recent series reported from Darwin
(Nickson et al., 2009) included 87 victims of whom 65% had
severe pain of rapid onset (<30 min) and 63% had visible
sting lesions. In this series, systemic features included
hypertension and ECG abnormalities among which were
atrial and ventricular ectopy, atrioventricular conduction
defects, ST-segment elevation, T-wave abnormalities and in
one case, ventricular tachycardia associated with cardio-
myopathy, acute pulmonary oedema and raised troponin
levels. Other serious sequelae included renal failure
(2 cases) and one case of pancreatitis and ileus. No patient
needed mechanical ventilation nor sustained intracerebral
haemorrhage. Nematocysts of variable morphology were
recovered from the skin of 7 patients, suggesting causation
by different species.
3.3. Hypertension
Although Barnes had observed hypertension in associ-
ation with the syndrome (Fenner et al., 1988), Fenner et al.
(1986a) speculated correctly that the hypertension may be
caused by catecholamine release in the victim. Hyperten-
sion (Ramasamy et al., 2005) and hypertension due to
catecholamine release (Tibballs et al., 2000; Winkel et al.,
2005) have been demonstrated in animal models of
C. barnesi envenomation. However, catecholamine excess
has yet to be confirmed in human cases. Although infusions
of phentolamine have been used successfully to combat
hypertension, a minute-to-minute ‘titratable’nitrate vaso-
dilator would be preferred if concurrent acute heart failure
exists. Fenner and Lewin (2003) proposed instigating
pre-hospital treatment of hypertension with sublingual
nitrates. This is currently recommended by the Queensland
Government Irukandji Taskforce in its guidelines for
the emergency management of the Irukandji syndrome
(Pereira et al., 2007).
3.4. Acute cardiac failure
In severe syndromic cases, a second phase occurs
approximately 6–18 h after a sting and includes cardiac
failure with pulmonary oedema. In this life-threatening
phase intensive medical therapy may be required with
oxygen, diuretics, mechanical ventilation and inotropic
support.
Cardiogenic pulmonary oedema has been described in
individual case reports (Fenner et al., 1988; Herceg, 1987;
Martin and Audley 1990; Mulcahy, 1999; Little et al.,
2001) and it occurred in 2 of a cohort of 62 victims pre-
senting to hospitals in Cairns (Little and Mulcahy, 1998). In
a retrospective review of 12 serious cases (Little et al.,
2003), pulmonary oedema was a regular feature after an
initial phase of mild skin pain followed 30 min after the
sting by considerable muscle pain and cramps, tachycardia
and hypertension. At a mean time of 14 h (range 1.5–18 h)
after the sting pulmonary oedema was evident radiologi-
cally and in some cases was associated with hypokinetic
cardiac dysfunction, reduced cardiac output and raised
serum cardiac enzymes. Required medical therapy included
oxygen, diuretics, vasodilators, inotropic support and
mechanical ventilation or application of continuous posi-
tive airway pressure (CPAP). However, in none of the cases
J. Tibballs et al. / Toxicon 59 (2012) 617–625620
was a positive identification made of a creature causing the
envenomation.
The mechanism of cardiac failure is speculative but two
possibilities exist. They may operate together. One putative
mechanism is “stress cardiomyopathy”secondary to hyper-
tension. Although it is curious that a relatively brief period of
hypertension (presumably due to release of catecholamines)
and in some cases its mediocrity is the sole cause of cardiac
failure in Irukandji syndrome victims, a sudden rise in
catecholamines may exert toxic effects on human car-
diocytes (Mann et al., 1992) resulting in catecholamine-
induced “stress cardiomyopathy”(Adameova et al., 2009).
This phenomenon is also recognised as ventricular apical
ballooning or “Takotsubo cardiomyopathy”(Lyon et al.,
2008; Zeb et al., 2011) or otherwise as regional myocardial
dysfunction (Hurst et al., 2006). Takotsubo cardiomyopathy
has occurred after a sting by another species of jellyfish,
Pelagia noctiluca (Bianchi et al., 2010).
A second putative mechanism of cardiac failure in Iru-
kandji syndrome is “membrane poration”. Considerable
scientific evidence shows that venoms of other jellyfish
create pores in cell membranes (Bailey et al., 2005;
Edwards et al., 2000, 2002; Edwards and Hessinger,
2000) which may disrupt cell function and allow ingress
of lethal toxins and egress of markers of cardiomyocyte
damage. Cell membrane poration may likewise be an action
of carybdeid toxins. This is supported by human cases of
human envenomation by carybdeids displaying elevated
serum troponin levels and ECG abnormalities (Little et al.,
2006). In some cases elevated troponin levels were not
related to hypertension. For example, a troponin I level of
6.4 mcg/L was associated with only a moderate level of
hypertension (170/100 mmHg) and normal echocardio-
graphic function (Corkeron et al., 2004) and in another case
a troponin I level of 5.5 mcg/L was associated with
moderate hypertension (170 mmHg) and “mid-ventricular
stress cardiomyopathy”(Tiong, 2009).
3.5. Other effects
On one occasion general Irukandji syndrome effects
were accompanied by loss of consciousness which was
attributed to cerebral oedema (Fenner and Heazlewood,
1997). Priapism has been reported in several case reports
(Nickson et al., 2009; Fenner and Carney, 1999).
3.6. Management of stings and envenomation
3.6.1. First-aid
Uniform first-aid for carybdeid stings is controversial.
Although domestic vinegar has been shown to inactivate
undischarged nematocysts of several species of jellyfish
including Chironex fleckeri (Hartwick et al., 1980), Carybdea
rastoni (Fenner and Williamson, 1987)(whose sting does
not cause Irukandji syndrome) and Tamoya sp (Fenner et al.,
1985), this has not been decisively demonstrated for
C. barnesi. Fenner et al. (1988) reported that vinegar
inhibited discharge of nematocysts from a small carybdeid,
resembling C. barnesi, captured where a case of Irukandji
syndrome had occurred 3 days previously. Although
Williamson et al. (1996) consequently recommended the
use of vinegar as first-aid for Irukandji syndrome, the
scientific evidence for this is deficient.
The analgesic effect of the application of heat or cold has
not been investigated scientifically for Carybdeid stings in
Australia but a randomised trial showed that immersion in
hot water was better than application of cold packs for
Physalia (Loten et al., 2006). Nonetheless, in Hawaii, hot
showers appeared to be analgesic for victims of Irukandji
syndrome (Yoshimoto and Yanagihara, 2002) while hot
water immersion of Carybdea alata (Alatina moseri) stings
provided better relief than applications of vinegar or
papain meat tenderiser (Nomura et al., 2002). A random-
ized placebo-controlled trial of the analgesic effect of hot
and cold packs on stings caused by C. alata (A. moseri)in
Hawaii showed a minimal trend towards pain relief after
10 min of hot pack application (Thomas et al., 2001). While
application of heat may be effective against local sting pain
of Australian species causing Irukandji syndrome, this
remains untested. Although lidocaine spray prevented
discharge of Chrysaora quinquecirrha and Physalia physalis
nematocysts and also relieved pain of stings of Atlantic
C. quinquecirrha and Chiropsalmus quadrumanus (Birsa
et al., 2010), it has not been tested with carybdeid stings.
3.6.2. Clinical management of envenomation
Pain relief and the treatment of hypertension and cardiac
failure are the most important features of management of
severe envenomation. In mild to moderate cases, pain relief
is the only issue. Jellyfish and other cnidarian venoms cause
pain by activation of transient receptor potential vanilloid-1
(TRPV1) non-selective cation channels expressed in nocio-
ceptive neurons (Cuypers et al., 2006). For analgesia,
repeated doses of parenteral opiates have been clinically
effective. The majority of cases in large series (Barnes,1964;
Little and Mulcahy 1998; Macrokanis et al., 2004; Nickson
et al., 2009) have required parenteral analgesia.
Corkeron (2003) used intravenous magnesium sulphate
(10 mmol loading dose followed by an infusion of 5 mmol/h
for 20 h) to achieve immediate pain relief and amelioration
of hyperadrenergic features (hypertension, agitation, dia-
phoresis, piloerection and dyspnoea) of Irukandji syndrome
in a victim stung by an unknown jellyfish. In a series of 10
victims with Irukandji syndrome, intravenous magnesium
salts provided pain relief and a reduction in blood pressure
(Corkeron et al., 2004). The rationale to treat hypertension
with magnesium is logically based on its ability to decrease
vascular resistance in hyperadrenergic states and to
suppress catecholamine release. Indeed, Mg
þþ
decreased
the force of contraction of vessels contracted by M. maxima
venom (Li, 2008; Li et al., 2011). However, the analgesic
effect of Mg
þþ
remains unexplained. It has been suggested
that since M. maxima venom appears to release the neuro-
sensory transmitter calcitonin gene-related peptide (CGRP)
(Evans et al., 2000) which is dependent on N-Type calcium
channels, the analgesic effect of Mg
þþ
may function by
competitive antagonism of calcium (Li, 2008; Li et al., 2011).
In severe cases of envenomation in which pulmonary
oedema and cardiac failure are present, admission to an
intensive care unit is needed. Mechanical ventilation or
CPAP and ‘titratable’inotropic and vasodilator therapy may
be required.
J. Tibballs et al. / Toxicon 59 (2012) 617–625 621
C. fleckeri antivenom appears ineffective. Although
C. fleckeri antivenom was observed to bind to a crude
venom preparation in vitro (Wiltshire et al., 2000), the
identity of the source Carybdeid in those experiments was
probably not C. barnesi (Gershwin, 2006a). C. fleckeri anti-
venom did not prevent tachycardia and vessel contraction
during C. barnesi venom provocation in vitro (Winkel et al,
2005) nor contraction of vessels caused by other carybdeids
including Alatina nr mordens (Winter et al., 2008) and
M. maxima (Li, 2008; Li et al., 2011). Fenner et al. (1986b)
showed that C. fleckeri antivenom was clinically ineffec-
tive in treatment of Irukandji syndrome. However, Barnes
had made that observation first when he inadvertently, and
ineffectively, used Chironex antivenom for the treatment of
what was, in retrospect, Irukandji syndrome in December
1970 (Winkel et al., 2003)
4. Other jellyfish causing Irukandji syndrome
Barnes predicted that the “Irukandji”syndrome would
be caused by a variety of species of jellyfish. Indeed, muscle
pain has been caused by species of Tamoya,Physalia and
Carybdea and other genera both in and outside Australian
waters (Williamson et al 1996; Yoshimoto and Yanagihara,
2002). Although several detailed case reports are available
(Cheng et al., 1999; Fenner et al., 1986a; 1986b; 1988;
Hadok, 1997; Herceg, 1987; Little et al., 2001; Little and
Seymour 2003; Martin and Audley 1990; Mulcahy, 1999)
on only one occasion was the victim able to offer
a description of an offending jellyfish. This was a 28-year-
old diver who experienced a typical Irukandji syndrome
after contact with a small box-shaped jellyfish with 4
tentacles with an overall size of a thumb. His sketch of the
animal closely resembled C. barnesi (Hadok, 1997).
4.1. Carybdea xaymacana
This small carybdeid is found along the Western
Australian coast (Gershwin, 2006a). Specimens captured
near Cairns are reported to have caused back pain, nausea,
sweating and hypertension among 5 children (Little, 2006;
Little et al., 2006), but the jellyfish may have been mistaken
for C. barnesi (Gershwin, 2006b). Experimentally, venom
derived from nematocyts of C. xaymacana caused elevation
of cytosolic Ca
þþ
in rat ventricular myocytes which was
blocked by lanthanum, a non-specific channel and pore
blocker, but not by verapamil, an L-type Ca
þþ
channel
antagonist (Bailey et al., 2005). Although it also caused
haemolysis of sheep and human erythrocytes, this effect
was not correlated with its lethality for Artemia sp. prawns.
Along with other jellyfish venoms (C. fleckeri,Chiropsalmus
sp.) examined by these investigators, it was speculated that
the lethality of C. xaymacana is due to cell membrane
poration.
4.2. Malo maxima
This species inhabits Indian Ocean waters in tropical
Western Australia, and is abundant offshore of the 80 Mile
Beach. It was identified in 2005 and superficially resembles
the related species, M. kingi, except that the bell is
somewhat taller –up to 5 cm (Fig. 1). This species is
probably one long-recognised by members of the pearl
diving industry in Broome as causing an Irukandji-like
syndrome, except that the sting is sharply painful
(Gershwin, 2005a).
Biochemical and pharmacological evidence suggests
that the cardiovascular effects of venom of M. maxima are
similar to that of the first jellyfish identified (C. barnesi)as
responsible for Irukandji syndrome. The venom appears to
stimulate the sympathetic but not parasympathetic
system (Li, 2008; Li et al., 2011). Analysis of crude venom
extracts (CVE) of M. maxima revealed a protein content and
sizes similar to those of C. barnesi. In rat tissues, CVE
increased contractility of atrial tissue which was not
diminished by atropine but which was diminished by pre-
treatment with propranolol, by the sodium channel
antagonist tetrodotoxin and by Mg
þþ
. The CVE also caused
contraction of small mesenteric arteries which was not
attenuated by
u
-conotoxin GVIA (N-type Ca
þþ
channel
antagonist) or Mg
þþ
and although also not attenuated by
prazosin (
a
1
–adrenoreceptor antagonist) was attenuated
by benextramine (
a
2
–adrenoreceptor antagonist) and by
C. fleckeri antivenom when the contraction was maximum.
Atrial rate was not increased by CVE unless accompanied
by Mg
þþ
. Pre-treatment with the calcitonin gene-related
peptide 8–37 (CGRP
8–37
), that is, a CGRP receptor antago-
nist, also decreased SVE-induced atrial contraction and
increased the sensitivity of mesenteric artery contraction
suggesting that the venom also causes release of the
neurosensory transmitter CGRP, which also has inotropic
effects. Since CGRP release is known to be dependent on
N-type calcium channels, it was speculated that the
mechanism of the apparent analgesic effect of magnesium
for Irukandji syndrome is via competitive antagonism of
calcium ions thus decreasing calcium influx with a reduc-
tion in release of CGRP.
4.3. Malo kingi
This species, in North Queensland Pacific waters, was
identified and named in 2007 (Gershwin, 2007). It has
a bell about 3 cm tall, half as wide and narrower at the apex
(Fig. 1) with mammillations (collections of stinging cells)
on the apex and on the walls of the bell. The 4 tentacles, one
at each pedalium (corner), are segmented by halo-like thin
sheet-rings perpendicular to the tentacle axis. Tentacular
nematocysts are found only on the halo rings. Nematocysts
found on the skin of Robert W King who died from jellyfish
sting-induced hypertension and intracranial haemorrhage
(Huynh et al., 2003) and after whom the species is named,
resembled those of M. kinghi (Gershwin, 2007). However,
as argued above (Section 3.2.1), the identity of the
responsible jellyfish remains uncertain but if it was
M. kingi, this species is patently harmful to humans.
4.4. Carukia shinju
This Carybdeid species has also been recently described
from waters off 80 Mile Beach, Broome, where it has
long been recognised as a source of jellyfish stings sus-
tained by pearl fishermen (Gershwin, 2005a). The species
J. Tibballs et al. / Toxicon 59 (2012) 617–625622
nomenclature “shinju”is a reference to the Japanese word
for “pearl”. Its bell is a rounded pyramid approximately
16 mm tall with warts (collections of nematocysts) scat-
tered over the apex. The four tentacles arising from each
corner have aggregations of nematocysts forming distinct
circular bands with an inferior margin greater in circum-
ference than the superior margin giving an appearance
described as “neckerchief-like tails”(Fig. 1). It is postulated
that this species, on the basis of its morphological and
genetic similarities, is a cause of a syndrome similar to that
produced by the Queensland C. barnesi (Gershwin, 2005a).
4.5. Alatina mordens, Alatina moseri
A. mordens was identified by Gershwin (2005b) (Fig. 1)
and linked to cases of Irukandji syndrome from Osprey Reef
near Cairns (Gershwin, 2005b; Little and Seymour, 2003;
Little et al., 2006). The venom derived from nematocysts
caused a long-lasting pressor response in anaesthetised
rats accompanied by large increases in their plasma
concentrations of adrenaline and noradrenaline (Winter
et al., 2008). The venom also contracted rat vas deferens
tissue but this was reduced by pre-treatment with
guanethidine (which blocks release of noradrenaline) or by
reserpine (which blocks transport of noradrenaline into
synaptic vesicles enabling it to be degraded by monoamine
oxidase). Whereas pre-treatment of rats with the
a
1
-adre-
noreceptor antagonist prazosin inhibited the pressor
response to venom, pre-treatment with the
b
-adrenor-
eceptor antagonist propranolol did not, thus suggesting
that
b
-adrenoreceptor blockade would not be useful in the
clinical treatment of hypertension. C. fleckeri antivenom
failed to inhibit effects of A. mordens venom (Winter et al.,
2008). A related species from Hawaii, A. moseri, formerly
known as C. alata or C. moseri, is also linked to Irukandji
syndrome (Yoshimoto and Yanagihara, 2002).
4.6. Gerongia rifkinae
This species inhabiting waters in Northern Territory and
Queensland was known previously as the “Darwin car-
ybdeid”and has been responsible for a mild form of Iru-
kandji syndrome (Currie, 2000a; 2000b; Currie and Wood
1995; O’Reilly et al., 2001; Williamson et al., 1996). It was
formally described and named in 2005 (Gershwin and
Alderslade, 2005). The bell is a robust cuboid, approxi-
mately 6 cm in height with a rounded apex. The four
tentacles, one at each corner, are round in cross-section
with an expansion (“flaring”) at their origins from the
base of the bell (Fig. 1).
4.7. Morbakka fenneri, “morbakka”
This jellyfish is also called the “Moreton Bay Stinger”or
the “Fire Jelly”. It is a relatively large carybdeid cubozoan
found in the Moreton Bay region near Brisbane (Fig. 1).
Although it closely resembles Tamoya virulenta (Williamson
et al., 1996) it has been recently classified as a species of
a new genus, Morbakka (Gershwin, 2008). Southcott
(1985) had previously proposed the common name “Mor-
bakka”–derived from “Moreton bay carybdeid medusa”.
Characteristically, the transparent bell is deeper than it is
wide with measurements of a large specimen being 11 cm
and 5–6 cm respectively (Gershwin, 2008; Fenner et al.,
1985). The four tapered tentacles are mauve in colour and
extend to 50 cm. At least two other similar jellyfish species
of Morbakka type exist but have not yet been studied
closely. A larger species with a bell height up to 18 cm and
width 14 cm is present in Queensland waters north of
Mackay and other species are present in waters off New
South Wales (Gershwin, 2008).
A sting raises a white wheal approximately 10 mm wide
and surrounded by a red flare resembling a superficial burn.
It is associated with severe burning pain of almost imme-
diate onset and lasts 24 h (Fenner et al., 1985). The
appearance of the lesion and the sensation give rise to the
common name “fire jelly”. There may also be associated
respiratory distress and throbbing lumbar pain (Williamson
et al., 1996) reminiscent of “Irukandji”syndrome. The
lesions show a characteristic tapering matching the tentacle
and with “ladder”markings similar to a chirodropid sting.
The skin lesions become pruritic, vesiculate and necrose.
The surface of the bell has nematocyts arranged in clusters
(warts) which causes multiple punctate lesions within an
area of erythema (Williamson et al., 1996). Typical undis-
charged and discharged nematocysts can be obtained from
skin scrapings. Undischarged nematocysts are inactivated
by vinegar (Fenner et al., 1985).
This species may cause a severe illness. A stung diver
experienced back and body pain accompanied by sweating,
nausea and hypertension. Hospitalisation was required for
2.5 days and ECG abnormalities with an elevated troponin l
level of 5.4 mcg/L were observed (Little et al., 2006).
5. Gaps in knowledge
Knowledge of carybdeids, their venoms and human
envenomation is very limited. Although eight named car-
ybdeids are regarded as causes of Irukandji syndrome,
numerous other carybdeids exist in waters World-wide
(Gershwin, 2006a; Williamson et al., 1996). It would not
be surprising to discover that many more carybdeids cause
human illness but their identification may be challenging.
Clinical identification of carybdeids, based solely on
macroscopic appearances of nematocysts recovered from
skin scrapings, is fraught with difficulty and unreliable.
It is difficult to replicate human envenomation in animal
models. The mechanism of actions of toxins deposited in
human epidermal tissue is virtually unknown. Jellyfish
stings deposit both venom and nematocyst components in
the victim’s skin. There may be immunological and well as
toxinological effects since nematocysts are composed of
collagen and chitin, both immunogenic materials (Tibballs
et al., 2011). While preparations of extracts from tentacles
are contaminated with non-nematocystic material, venom
derived from nematocyst discharge is probably devoid of
nematocystic components. Moreover, nematocysts derived
from different C. barnesi components, i.e., tentacles vs bell,
may have different actions, and nematocysts present in
different life cycle stages of a species may differ and
their toxins may have different actions (Underwood and
Seymour, 2007)
J. Tibballs et al. / Toxicon 59 (2012) 617–625 623
The mechanisms of actions of jellyfish toxins are poorly
understood. Although some species of jellyfish, including
C. xaymacana, seem to cause pore formation in cell
membranes (Bailey et al., 2005; Edwards et al., 2000;
2002), the mechanism whereby this occurs is unknown.
Actions on membrane conductivity and ion channels are
likewise virtually unknown.
The circumstances leading to carybdeid envenomation
syndrome are unclear. Weather and sea conditions favour-
ing jellyfish envenomation are unpredictable (Fenner and
Harrison, 2000). Even the life-cycles and location of jelly-
fish species causing Irukandji syndrome are obscure.
The medical treatment of Irukandji syndrome, in phar-
macological terms, is basic. While pain and hypertension
may be treated with common agents, a venom-targeted
treatment of cardiac failure is lacking. There is need for
extensive investigation of the actions of venom to derive
specific treatments which may derogate the need for
antivenoms.
6. Conclusions
Numerous Australian jellyfish of the Order Carybdeidae,
typified by C. barnesi, are able to cause significant human
illness in a syndrome clinically known as “Irukandji
syndrome”. The syndrome is characterised by a sting of
minor severity followed at an interval by the onset of severe
muscle pains especially of the lower back, muscle cramps,
vomiting, sweating, agitation, vasoconstriction, prostration
and hypertension. Mild cases of envenomation are treatable
with analgesic agents but the syndrome may progress to
acute cardiac failure and necessitate medical treatment
with antihypertensive agents and mechanical ventilation.
Magnesium appears to be beneficial for treatment of pain
and hypertension. The mechanism of serious injury is
poorly understood but it includes release of endogenous
catecholamines and possibly poration of myocardial cellular
membranes leading to acute heart failure.
Conflict of interest
None.
References
Adameova, A., Abdellatif, Y., Dhalla, N.S., 2009. Role of excessive amounts
of circulating catecholamines and glucocorticoids in stress-induced
heart disease. Can. J. Physiol. Pharmacol. 87, 493–514.
Bailey, P.M., 2003. Fatal envenomation by jellyfish causing Irukandji
syndrome. Med. J. Aust. 178, 139–140.
Bailey,P.M.,Bakker,A.J.,Seymour,J.E.,Wilce,J.A.,2005.Afunctional
comparison of the venom of three Australian jellyfish –Chironex
fleckeri, Chiro psalm us sp., and Carybdea xaymacana –on cytosolic
Ca
2þ
, haemolysis and Artemia sp.lethality.Toxicon45,233–242 .
Barnes, J.H., 1964. Cause and effect in Irukandji stingings. Med. J. Aust. 1,
897–904.
Barnes, J.H., 1966. Studies on three venomous Cubome dusae. In:
Rees, W.J. (Ed.), The Cni daria and Their Evolution. Academic Press,
New York.
Bentlage, B., Cartwright, P., Yanagihara, A.A., Lewis, C., Richards, G.S.,
Collins, A.G., 2010. Evolution of box jellyfish (Cnidaria: Cubozoa),
a group of highly toxic invertebrates. Proc. R. Soc. Lond. B. Biol. Sci.
277, 493–501.
Bianchi, R., Torella, D., Spaccarotella, C., Mongiardo, A., Indolfi, C., 2010.
Mediterranean jellyfish sting-induced Tako-Tsubo cardiomyopathy.
Eur. Heart J. doi:10.1093/eurheartj/ehq349.
Birsa, L.M., Verity, P.G., Lee, R.F., 2010. Evaluation of the effects of various
chemicals on discharge of and pain caused by jellyfish nematocysts.
Comp. Biochem. Physiol. Part C 151, 426–430.
Cheng, A.C., Winkel, K.D., Hawdon, G.M., McDonald, M., 1999. Irukandji-
like syndrome in Victoria. Aust. NZ. J. Med. 29, 835.
Cleland, J.B., Southcott, R.V., 1965. Injuries to Man from Marine Inverte-
brates in the Australian Region. Nat. Health Med. Res. Council,
Canberra. Special Report, Series no. 12.
Corkeron, M.A., 2003. Magnesium infusion to treat Irukandji syndrome.
Med. J. Aust. 178, 411.
Corkeron, M., Pereira, P., Makrocanis, C., 2004. Early experience with
magnesium administration in Irukandji syndrome. Anaesth. Intens.
Care 32, 666–669.
Currie, B., Wood, Y.K., 1995. Identification of Chironex fleckeri enveno-
mation by nematocyst recovery from skin. Med. J. Aust. 162, 478–480.
Currie, B., 2000a. Box-jellyfish –an update from the Northern Territory
and the NT Chironex fleckeri treatment protocol. Northern Territory
Dis. Control Bull. 7, 7–8.
Currie, B., 200 0b. Clinical toxicology: a tropical Australian perspective.
Ther. Drug Monit. 22, 73–78.
Cuypers, E., Yanagihara, A., Karlsson, E., Tytgat, J., 2006. Jellyfish and other
cnidarian envenomations cause pain by affecting TRPV1 channels.
FEBS Lett. 580, 5728–5732.
Dawson, A.H., 2003. Fatal envenomation by jellyfish causing Irukandji
syndrome. Med. J. Aust. 178, 139.
de Pender, A.M.G., Winkel, K.D., Ligthelm, R.J., 2006. A probable case of
Irukanji syndrome in Thailand. J. Travel Med. 13, 240–243.
Edwards, L., Hessinger, D.A., 2000. Portuguese Man-of-war (Physalia
physalis) venom induces calcium influx into cells by permeabilizing
plasma membranes. Toxicon 38, 1015–1028.
Edwards, L.P., Whitter, E., Hessinger, D.A., 2002. Apparent membrane
pore-formation by Portuguese Man-of-war (Physalia physalis).
Toxicon 40, 1299–1305.
Edwards, L., Luo, E., Hall, R., Gonzalez Jr., R.R., Hessinger, D.A., 2000. The
effect of Portuguese man-of-war (Physalia physalis) venom on
calcium, sodium and potassium fluxes of cultured embryonic chick
heart cells. Toxicon 38, 323–335.
Evans, B.N., Rosenblatt, M.I., Mnayer, L.O., Oliver, K.R., Dickerson, I.M.,
2000. CGRP-RCP, a novel protein required for signal transduction
at a calcitonin gene-related peptide and adrenomedullin receptors. J.
Clin. Chem. 275, 31438–31443.
Fenner, P.J., 2004. Sublingual glycerol trinitrate as prehospital treatment for
hypertension in Irukandji syndrome (letter). Med.J. Aust. 180,483–484.
Fenner, P., Carney, I., 1999. The Irukandji syndrome. A devastating
syndrome caused by a north Australian jellyfish. Aust. Fam. Phys. 28,
1131 –1137.
Fenner, P.J., Fitzpatrick, P.F., Hartwick, R.J., Skinner, R., 1985. “Morbakka”,
another cubomedusan. Med. J. Aust. 143, 550–555.
Fenner, P.J., Hadok, J.C., 2002. Fatal envenomation by jellyfish causing
Irukandji syndrome. Med. J. Aust 177, 362–363.
Fenner, P.J., Hadok, J.,C., 2003. Fatal envenomation by jellyfish causing
Irukandji syndrome. Med. J. Aust. 178, 139–140.
Fenner, P.J., Harrison, S.L., 2000. Irukandji and Chironex fleckeri jellyfish
envenomation in tropical Australia. Wilderness Environ. Med. 11,
233–240.
Fenner, P.J., Heazlewood, R.J., 1997. Papilloedema and coma in a child:
undescribed symptoms of “Irukandji”syndrome. Med. J. Aust. 167,
650–651.
Fenner, P.J., Lewin, M., 2003. Sublingual glyceryl trinitrate as prehospital
treatment for hypertension in Irukandji syndrome (letter). Med. J.
Aust. 179, 655.
Fenner, P.J., Rodgers, D., Williamson, J., 1986b. Box jellyfish antivenom and
“Irukandji”stings. Med. J. Aust. 144, 665–666.
Fenner, P.J., Williamson, J.A., Burnett, J.W., Colquhoun, D.M., Godfrey, S.,
Gunawardane, K., Murtha, W., 1988. The “Irukandji syndrome”and
acute pulmonary oedema. Med. J. Aust. 149, 150–155.
Fenner, P.J., Williamson, J., 1987. Experiments with the nematocysts of
Carybdea rastoni (“Jimble”). Med. J. Aust. 147, 258–259.
Fenner, P.J., Williamson, J., Callanan, V.I., Audley, I., 1986a. Further
understanding of, and a new treatment for, “Irukandji”(Carukia
barnesi) stings. Med. J. Aust. 145, 569–574.
Flecker, H., 1945. Injuries caused by unknown agents to bathers in north
Queensland. Med. J. Aust. 2, 128.
Flecker, H., 1952. Irukandji sting to North Queensland bathers without
production of weals but with severe general symptoms. Med. J. Aust.
2, 89–91.
Gershwin, L.-A., 2005a. Two new species of jellyfishes (Cnidaria: Cubo-
zoa: Carybdeida) from tropical Western Australia, presumed to cause
Irukandji Syndrome. Zootaxa 1084, 1–30.
J. Tibballs et al. / Toxicon 59 (2012) 617–625624
Gershwin, L., 2005b. Carybdea alata auct. and Manokia Stiasnyi, reclassi-
fication to a new family with description of a new genus and two new
species. Mem. Queensland Museum 51, 501–523.
Gershwin, L.-A., 20 06a. Nematocysts of the Cubozoa. Zootaxa 1232, 1–57.
Gershwin, L., 2006b. Jellyfish responsible for Irukandji syndrome. Q. J.
Med. 99, 801–802.
Gershwin, L.-A., 2007. Malo kingi: a new species of Irukandji jellyfish
(Cnidaria: Cubozoa: Carybdeida), possibly lethal to humans, from
Queensland, Australia. Zootaxa 1659, 55–68.
Gershwin, L., 2008. Morbakka fenneri, a new genus and species of Iru-
kandji jellyfish (Cnidaria: cubozoa). Mem. Queensland Museum –Nat.
54, 23–33.
Gershwin, L.-A., Alderslade, P., 2005. A new genus and species of box
jellyfish (Cubozoa: Carybdeidae) from tropical Australian waters.
The Beagle 21, 27–36.
Grady, J.D., Burnett, J.W., 2003. Irukandji-like syndrome in South Florida
divers. Ann. Emerg. Med. 42, 763–766.
Hadok, J.C., 1997. “Irukandji”syndrome: a risk for divers in tropical
waters. Med. J. Aust. 167, 649–650.
Hartwick, R., Callanan, V., Wil liamson, J., 1980. Disarming the box
jellyfish. Nematocyst inhibition in Chironex flecker i. Med. J. Aust . 1,
15–20.
Herceg, I., 1987. Pulmonary oedema following an Irukandji sting. SPUMS J.
17, 95.
Hurst, R.T., Askew, J.W., Reuss, C.S., et al., 2006. J. Am. Coll. Cardiol. 48,
579–583.
Huynh, T.T., Seymour, J., Pereira, P., Mulcahy, R., Cullen, P., Carrette, T.,
Little, M., 2003. Severity of Irukandji syndrome and nematocyst
identification from skin scrapings. Med. J. Aust. 178, 38–41.
Li, R., 2008. The in vitro cardiovascular pharmacology of Malo maxima:
a species of box jellyfish suspected of causing Irukandji syndrome in
the Broome region of Western Australia. Bachelor of Medical Science
Thesis, The University of Melbourne.
Li, R., Wright, C.E., Winkel, K.D., Gershwin, L.A., Angus, J.A., 2011. The
pharmacology of Malo maxima jellyfish venom extract in isolated
cardiovascular tissues: a probable cause of the Irukandji syndrome in
Western Australia. Toxicol. Lett. 201, 221–229.
Little, M., 2006. Response to letters on Jellyfish responsible for Irukandji
syndrome. Q. J. Med. 99, 803–804.
Little, M., Mulcahy, R.F., 1998. A year’s experience of Irukandji enveno-
mation in far north Queensland. Med. J. Aust. 169, 638–641.
Little, M., Mulcahy, R.F., Wenck, D.J., 2001. Life-threatening cardiac failure
in a healthy young female with Irukandji syndrome. Anaesth. Intens.
Care 29, 178–180.
Little, M., Pereira, P., Carrette, T., Seymour, J., 2006. Jellyfish responsible
for Irukandji syndrome. Q. J. Med. 99, 425–427.
Little, M., Pereira, P., Mulcahy, R., Cullen, P., Carrette, T., Seymour, J., 2003.
Severe cardiac failure associated with presumed jellyfish sting. Iru-
kandji syndrome? Anaesth. Intens. Care 31, 642–647.
Little, M., Seymour, J., 2003. Another cause of “Irukandji stingings”. Med. J.
Aust. 179, 654–656.
Loten, C., Stokes, B., Worsley, D., Seymour, J.E., Jiang, S., Isbister, G.K., 2006.
A randomised controlled trial of hot water (45
C) immersion versus
ice packs for pain relief in bluebottle stings. Med. J. Aust. 184, 329–
333.
Lyon, A.R., Rees, P.S., Prasad, S., Poole-Wilson, P.A., Harding, S.E., 2008.
Stress (Takotsubo) cardiomyopathy –a novel pathophysiological
hypothesis to explain catecholamine-induced acute myocardial
stunning. Nat. Clin. Pract. Cardiovasc. Med. 5, 22–29.
Macrokanis, C.J., Hall, N.L., Mein, J.K., 2004. Irukandji syndrome in
northern Western Australia: an emerging health problem. Med. J.
Aust. 18, 699–702.
Mann, D.L., Kent, R.L., Parsons, B., Cooper IV, G., 1992. Adrenergic effects
on the biology of the adult mammalian cardiocyte. Circulation 85,
790–804.
Martin, J.C., Audley, I., 1990. Cardiac failure following Irukandji enveno-
mation. Med. J. Aust. 153, 164–166.
Mulcahy, R., 1999. A severe case of Irukjandji syndrome. Winter Sympo-
sium, Australasian College for Emergency Medicine, July, Lorne,
Australia. p. 88.
Mulcahy, R., Little, M., 1997. Thirty cases of Irukandji envenomation from
far north Queensland. Emerg. Med. 9, 297–299.
Nickson, C.P., Waugh, E.B., Jacups, S.P., Currie, B.J., 2009. Irukandji
syndrome case series from Australia’s tropical northern territory. Ann.
Emerg. Med. 54, 395–403.
Nomura, J.T., Sato, R.L., Ahern, R.M., Snow, J.L., Kuwaye, T.T., Yamamoto, L.
G., 2002. A randomized paired comparison trial of cutaneous
treatments for acute jellyfish (Carybdea alata) stings. Am. J. Emerg.
Med. 20, 624–626.
O’Reilly, G.M., Isbister, G.K., Lawrie, P.M., Treston, G.T., Currie, B.J., 2001.
Prospective study of jellyfish stings from tropical Australia, including
the major box jellyfish Chironex fleckeri. Med. J. Aust. 175, 652–655.
Pereira, P., Barry, J., Corkeron, M., Keir, P., Little, M., Seymour, J., 2010.
Intracranial haemorrhage and death after envenoming by the jellyfish
Carukia barnesi. Clin. Toxicol. 48, 390–392.
Pereira, P., Corkeron, M., Little, M., Farlow, D., 2007. Irukandji Taskforce
Guidelines for the Emergency Management of Irukandji Syndrome.
Prevention and Response Working Group of the Irukandji Taskforce,
Queensland Government. <http://archive.rubicon-foundation.org/
9372>.
Pommier, P., Coulange, M., De Haro, L., 2005. Envenimation systémique
par meduse en Guadeloupe: Irukandji-like syndrome. Med. Trop.
(Mars) 65, 357–359.
Ramasamy, S., Isbister, G.K., Seymour, J.E., Hodgson, W.C., 2005.
The in vivo cardiovascular effects of the Irykandji jellyfish (Carukia
barnesi) nematocyst venom and a tentacle extract in rats. Toxicol. Lett.
155, 135–141.
Salam, A.M., Albinali, H.A., Gehani, A.A., Al Suwaidi, J., 2003. Acute
myocardial infarction in a professional diver after jellyfish sting. Mayo
Clin. Proc. 78, 1557–1560.
Southcott, R.V., 1952. Fatal stings to north Queensland bathers. Med. J.
Aust. 1, 272.
Southcott, R.V., 1956. Studies on Australian Cubomedusae, including
a new genus and species apparently harmful to man. Aust. J. Mar.
Freshw. Res. 7, 254–280.
Southcott, R.V., 1967. Revision of some Carybdeidae (Scyphozoa: Cubo-
medusae), including a description of the jellyfish responsible for the
‘Irukandji syndrome’. Aust. J. Zool. 15, 651–671.
Southcott, R.V., 1985. “The “morbakka”. Med. J. Aust. 143, 324.
Thomas, C.S., Scott, S.A., Galanis, D.J., Goto, R.S., 2001. Box jellyfish (Car-
ybdea alata) in Waikiki: their influx cycle plus the analgesic effect of
hot and cold packs on their stings to swimmers at the beach:
a randomized, placebo-controlled, clinical trial. Hawaii Med. J. 60,
100 –107.
Tibballs, J., Hawdon, G., Winkel, K.D., Wiltshire, C., Lambert, G., Gershwin,
L.A., Fenner, P.J., Angus, J.A., 2000. The in vivo cardiovascular effects of
Irukandji (Carukia barnesi) venom. XIIIth World Congress of the
International Society of Toxinology. 18–22 September, Paris, P276.
Tibballs, J., Yanagihara, A., Turner, H., Winkel, K., 2011. Immunological and
toxinological responses to jellyfish stings. Inflamm. Allergy –Drug
Targets 10, 438–446.
Tiong, K.T., 2009. Irukandji syndrome, catecholamines, and
mid-ventricula r stress cardiomyopathy. Eur. J. Echocardiography 10,
334–336.
Underwood, A.H., Seymour, J.E., 2007. Venom ontogeny, diet and
morphology in Carukia barnesi, a species of Australian box jellyfish
that causes Irukandji syndrome. Toxicon 49, 1073–1082.
Williamson, J.A., Fenner, P.J., Burnett, J.W., Rifkin, J.F., 1996. Venomous &
Poisonous Marine Animals: A Medical and Biological Handbook. Surf
Life Saving Australia and University of New South Wales Press,
Sydney.
Wiltshire, C.J., Sutherland, S.K., Fenner, P.J., Young, A.R., 2000. Optimiza-
tion and preliminary characterization of venom isolated from three
medically important jellyfish: box jellyfish (Chironex fleckeri),
Irukandji (Carukia barnesi) and blubber (Catostylus mosaicus).
Wilderness Environ. Med. 11, 241–250.
Winkel, K., Hawdon, G., Fenner, P.J., Gershwin, L.-A., Collins, A.G.,
Tibballs, J., 2003. Jellyfish antivenoms: past, present and future. J.
Toxicol-Toxin Rev. 22, 13–25.
Winkel, K.D., Tibballs, J., Molenaar, P., Lambert, G., Coles, P., Ross-Smith, M.
, Wiltshire, C., Fenner, P., Gershwin, L.-A., Hawdon, G.M., Wright, C.E.,
Angus, J.A., 2005. The cardiovascular actions of the venom from the
Irukandji (Carukia barnesi) jellyfish: effects in human, rat and guinea
pig tissues in vitro, and in pigs in vivo. Clin. Exp. Pharmacol. Physiol.
32, 777–788.
Winter, K.L., Isbister, G.K., Schneider, J.J., Konstantakopoulos, N.,
Seymour, J.E., Hodgson, W.C., 2008. An examination of the cardio-
vascular effects of an ‘Irukandji’jellyfish, Alatina nr mordens. Toxicol.
Lett. 179, 118–123.
Yoshimoto, C.M., Yanagihara, A.A., 2002. Cnidarian (coelenterate) enve-
nomations in Hawaii improve following heat application. Trans. R.
Soc. Trop. Med. Hyg. 96, 300–303.
Zeb, M., Samba, N., Scott, P., Curzen, N., 2011. Takotsubo cardiomyopathy:
a diagnostic challenge. Postgrad. Med. J. 87, 51–59.
J. Tibballs et al. / Toxicon 59 (2012) 617–625 625
