Box jellyfish Chironex fleckeri stings pose a serious public health threat in the Philippines. Cases were

reported to have caused dermal necrosis and infections. The nephrotoxicity of the venom of Chironex fleckeri

has been attributed to hemolysis, oxidative stress, and inflammation, which lead to acute kidney injury.

Despite numerous studies on the mechanisms involved with the venom, not much is known to this date about

its overall contribution to either treatment efficacy or kidney dysfunction. A descriptive review of mechanisms

of venom, diagnostic approaches, and treatments in the Philippine setting will help highlight the deficit in

pertinent public health policies. Chironex fleckeri is likely to be found in the coastal and estuarine areas of the

Philippines. Distribution is influenced by seasonal water temperature and salinity, mirroring conditions found

in its native Australian waters. Such risk factors can include the physical characteristics of this jellyfish, a

transparent, cube-shaped bell with long, venomous tentacles, which will deliver potent venom. Knowing where

potential seriousness and a lack of extensive data on the incidence. Given the notoriety for highly toxic venom,

box jellyfish often live in areas that receive a large number of tourists, thus exposing people to its dangers.

There are recommendations on population surveillance—mostly for the Department of Agriculture and local

governments [1]. During 2008–2013, 57 probable cases were recorded; most suffered minor to severe

complications from the stings, which included dermal necrosis and infections [2]. Such incidents raise concern

in order to strengthen monitoring and create public awareness for measures against the risks caused by jellyfish

stings.

The venom of Chironex fleckeri contains at least 250 proteins, comprising metalloproteinases and pore-

forming toxins that contribute to its tissue-destroying and systemic effects [3, 4]. Specific host factors, such as

the ATP2B1 protein, have been critical for venom-induced cytotoxicity; thus, implying specific pathways also

documented, especially in tropical nations such as the Philippines [8]. Current treatments, such as plasma

exchange and renal replacement therapy, have some evidence but have not been proven in box jellyfish sting

settings [8]. Public awareness and education of health workers may enhance case identification and recording,

that will then serve as the basis of any future database and research and policy-making [1].

These research gaps notwithstanding, a comprehensive review article synthesizing the existing knowledge on

Chironex fleckeri toxins and its management is truly warranted, especially in the Philippine context. The said

review will highlight the peculiar challenges of this condition within the country's box jellyfish envenomation,

with implications that will be useful for health professionals, researchers, and policymakers. In combining data

from studies on the mechanisms of venom, treatment strategies, and preventive measures, this review may also

prove useful for improving public health interventions and the outcomes of patients.

The geographical distribution of Chironex fleckeri, the Australian box jellyfish, is influenced by multiple

ecological and environmental factors in Philippine waters. Although considered to be related mainly to

northern tropical waters in Australia, its incidence in the Philippines is most probably linked with similar

coastal and estuarine settings. C. fleckeri generally inhabits shallow waters and is often times found in

mangrove creeks and coastal beaches; these are common in the Philippines [9]. It is probably associated with

areas characterized by rich filter feeder assemblages; thus, C. fleckeri might also share similar ecological

niches in the waters of the Philippines [9].

Occurrences of C. fleckeri are highly seasonal, with large populations during summer months, while a similar

seasonal pattern could take place in the Philippines, considering the country generally experiences similar

Distribution of Chironex fleckeri, the Australian box jellyfish, remains largely undocumented in the

Philippines, although it is certainly in coastal conditions similar to its native habitats; this species probably

occurs in northern coastal areas, especially in regions like Cagayan Valley, Ilocos Norte, and the province of

Aurora, where warm, shallow waters are dominant [12, 13]. Warm waters are prominent in the Cagayan Valley

in the north, making the area suitable for C. fleckeri [12]. Also, Ilocos Norte and Aurora display shallow

coastal conditions with warm temperatures that may generally support the species' occurrence [14].

Tropical climates and estuarine zones hosting mangrove forests are abundant in the Visayan Sea and areas of

Eastern Visayas, including Leyte and Samar, all of which provide natural ecosystems for box jellyfish [15].

In Mindanao, coastal areas such as Davao and Zamboanga have rich marine biodiversity and are generally

warm in temperature, thus becoming the candidate sites for C. fleckeri [16]. Considering that coral reefs and

documented. The majority of the existing studies on C. fleckeri have focused on its range in Australia, leaving

a substantial gap in understanding its occurrence, seasonality, and population dynamics in the Philippines.

While regions like Cagayan Valley, Ilocos Norte, Aurora, and parts of Visayas and Mindanao have suitable

habitats for this species—warm, shallow waters with a rich assemblage of filter feeders—empirical data

confirming its presence, distribution patterns, or ecological impacts are lacking. Also, possible interactions

between C. fleckeri and other jellyfish species, like Catostylus purpurus, in these ecosystems remain

unexplored. Such a knowledge gap limits the capacity to assess the risks of envenomation incidents, design

mitigation strategies, and understand the ecological role that the species plays in Philippine marine

environments. Further research is needed to ascertain its presence, distribution, and possible influence on local

marine biodiversity.

The bell of Chironex fleckeri is usually pale blue and transparent, with a diameter of approximately 16 cm (6.3

in), although it can grow up to 35 cm (14 in) [18]. Its cube-like shape is characteristic of the species, which is

tentacle can have as many as 5,000 stinging cells, which are triggered both by physical pressure and by

chemical signals from potential prey [18].

Chironex fleckeri possesses well-developed sensory systems compared to other jellyfish species. Arranged

around its bell are four rhopalia, each containing six eyes—making a total of 24 individual eyes [20]. Light can

be perceived by these eyes, and together, they may even provide the jellyfish with the ability to form images; it

is still unclear how those tremendous amounts of visual input are processed without a brain [19]. Especially

attractive for this jellyfish are different colors of light; it is most sensitive to blue light, which, if detected, can

influence its feeding behavior by making it slow down its pulsation rate and extend its tentacle [18]. Unlike the

majority of jellyfish, which simply drift with the tides, C. Fleckeri can swim actively, and by contracting its

bell, it can propel itself at speeds of up to four knots—roughly 7.4 km/h or 4.6 mph [20]. This helps it search

Chironex fleckeri venom has been characterized, and there are several potent toxins involved, including

Phospholipase A2, CfTX-1, CfTX-A, CfTX-B, and CfTX-2. Most of their deleterious actions are primarily as

hemolytic, cytotoxic, and nephrotoxic effects. These potent toxins cause a massive breakdown of erythrocytes,

leading to severe clinical manifestations, including pain, skin necrosis, fever, vomiting, and even respiratory

failure due to the mentioned activities of venom toxins [18, 19]. The main cause of renal impairment was

attributed to massive intravascular hemolysis, with resultant free hemoglobin and toxic metabolites entering

the circulation in very large quantities and overwhelming the mechanisms of renal filtration, causing AKI to

the victim [20]. Moreover, besides hemolysis, CfTX-2 had other cardiotoxic and cytotoxic properties,

complicating envenoming [18, 19]. Treatment may be done using vinegar and seawater application to

red blood cells. This leads to acute kidney injury (AKI) through hemolysis and the consequent release into

circulation of toxic byproducts of hemolysis, such as free hemoglobin. This overwhelms renal filtration and

causes oxidative stress within renal tissues, leading to AKI [20]. Envenoming by C. fleckeri may present with

immediate severe symptoms, which include severe pain at the site of the sting followed by systemic reactions,

such as fever and vomiting, that may necessitate urgent medical intervention to prevent life-threatening

complications [19].

CfTX-1, one of the major toxins in the venom of the box jellyfish (Chironex fleckeri), has been known to

cause cell destruction, especially to red blood cells, causing hemolysis. Hemolytic activity contributes to many

clinical manifestations, such as severe pain, fever, and vomiting, although less is reported in the literature

regarding specific clinical effects attributed to CfTX-1 itself [18, 19]. The main route by which this toxin

CfTX-2, a complex toxin contained in the venom of the box jellyfish (Chironex fleckeri), demonstrates

cardiotoxic, cytotoxic, and nephrotoxic activities that can produce severe symptoms due to systemic

engagement of multiple organs and potentially leading to heart and kidney failure [18, 19]. Its toxic effects are

generally exerted through disruption of cellular membranes and cellular lysis, which includes destruction of

red blood cells contributing to free hemolysis and subsequent nephrotoxicity [20]. Envenoming by C. fleckeri

is usually characterized by immediate, very severe symptoms—namely, extreme pain locally where the sting

occurred, fever, and vomiting, underscoring the need for urgent medical attention [19]. The mechanism

renal tissues and aggravates AKI [25]. NADPH oxidase 4 (Nox4) is one major source of reactive oxygen

species (ROS) production within kidneys, and there is evidence to show that inhibiting this can be protective

against heme‐induced kidney injury [18, 25].