Introduction

Snakebite envenomation is an important but often under-reported public health hazard in many countries including Malaysia. The Naja (cobras) and Bungarus (kraits) species are the leading causes of severe envenomation and mortality in Asia [1–3]. Cobras, belonging to the genus Naja, has the potential to cause permanent disability and death in humans. Presently, there are 11 cobra species indigenous to South and Southeast Asia, however, the taxonomy of this genus remains unsettled, with ongoing descriptions of new species. In Malaysia, the most common cause for venomous snake bites is from cobra species, Naja sumatrana and Naja kaouthia (Fig 1) [4–8].

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Fig 1. Morphological features of N. kaouthia and N. sumatrana.

(A) Ventral view of N. kaouthia. Image credit: M.K. Arif. (B) Dorsal view of N. kaouthia. Image credit: M.K. Arif. (C) Ventral view of N. sumatrana. Image credit: M.K. Arif. (D) Dorsal view of N. sumatrana. Image credit: M.K. Arif.

https://doi.org/10.1371/journal.pntd.0013271.g001

Cobra species possess potent postsynaptic neurotoxic venoms, with some exhibiting cytotoxic and cardiotoxic effects [9–12]. Their venom is rich in three-finger toxins (3FTx), including polypeptides of neurotoxins and cardiotoxins, as well as phospholipase A2 (PLA2) [13,14]. Envenomation can result in post-synaptic blockade and inhibiting neuromuscular transmission, leading to symptoms such as ptosis, ophthalmoplegia, dysphagia and impairment of skeletal muscles contractility and paralysis. [15,16]. Patients may experience nasal voice, difficulty swallowing, and respiratory failure, and generalized flaccid paralysis which can be fatal [17]. In addition, painful progressive tissue swelling, and necrosis (dermonecrosis), are common manifestations [9,18].

Remote Envenomation Consultation Services (RECS) is a specialized online risk management support system that assists doctors in managing clinical toxicology-related cases. It was founded in early 2012 [10]. RECS offers a 24-hour on-call consultation service through a smart text messaging platform while adhering to guidelines set by the Ministry of Health Malaysia (MOH) [19]. RECS consultants are affiliated with the Malaysian Society of Toxinology and the special interest group of the College of Emergency Physician Malaysia. RECS maintains detailed consultation logs that include validated management recommendations and images of the offending animals, with species identification verified by subject matter experts.

Identifying snake species and recognizing the clinical features of envenomation is the main concern among doctors managing snake-related injuries. Poor clinical management may cause mortality and morbidity affecting the cost for health expenditure and human lives. This study is important in facilitating optimal clinical management and at the same time minimizing the cost and wastage of resources. The objective of this study was to analyze the frequency, geographical distribution, clinical features, treatments, and outcomes of Naja species-related injuries in Malaysia consulted to RECS.

Methods

Results

From 4474 RECS consultations, 1070 (23.9%) were in 2020, 1014 (22.7%) in 2021, 1019 (22.8%) in 2022 and 1371 (30.6%) in 2023. The annual frequency of cases appears similar during COVID-19 pandemic phase (2020–2021) and the transition year 2022 (endemic phase). There appears to be an increase of outdoor incidents during the endemic (55.4%) years compared to pandemic (50.4%) years while there were fewer indoor cases during the pandemic (49.6%) years compared to endemic (44.6%) years. A total of 512 Naja species related cases were diagnosed within the study period with 254 (49.6%) from 2020-2021 and 258 (50.4%) from 2022-2023. In 2023, N. sumatrana related cases appear to be higher than previous years (Fig 2).

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Fig 2. Frequency and diagnosis of Naja spp. related injuries consulted to RECS from 2020-2023.

The consultations with RECS remained similar during COVID-19 pandemic and endemic phase.

https://doi.org/10.1371/journal.pntd.0013271.g002

Most patients were male (n = 358, 69.9%). The mean age was 36.2 years (SD ± 20.7) with the youngest was nine months and the oldest was 87 years (Table 1). Malaysians (n = 424, 82.8%) were the majority. Most injuries were non-occupational related (n = 433, 84.6%). The incident mostly occurred in the afternoon (n = 220, 43.0%), and in outdoor setting (n = 265, 51.8%).

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Table 1. Demographic characteristics of Naja species related injuries consulted to RECS from 2020–2023.

https://doi.org/10.1371/journal.pntd.0013271.t001

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Fig 3. Geographical distribution of confirmed Naja spp. related injuries patients.

Most N. sumatrana cases were from Johor and N. kaouthia cases were from Selangor. There were also N. kaouthia cases from Pahang, Terengganu, Johor, Negeri Sembilan and Sarawak. Base map static image and data from OpenStreetMap and OpenStreetMap Foundation. (Copyright OpenStreetMap contributors, https://www.openstreetmap.org/#map=6/4.23/108.24).

https://doi.org/10.1371/journal.pntd.0013271.g003

The diagnosis was categorized as: Naja sumatrana bite (n = 144, 28.1%); Naja kaouthia bite (n = 121, 23.6%); Undifferentiated Naja species bite (n = 184, 36.0%); Naja sumatrana venom ophthalmia (n = 61, 11.9%); Naja sumatrana bite & venom ophthalmia (n = 2, 0.4%). Most of the patients were bitten once (n = 437, 96.9%) (Table 2). The lower limb was the most common anatomical region affected (n = 267, 52.1%). Tourniquet application was the most frequent first aid (pre-hospital) intervention (n = 154). The median bite to door (BTD) time was 1 h (IQR: 0–2 h) with the maximum delay of 21 hr. Most Naja species bite patients only developed local envenomation (n = 366, 81.2%) with 75 (16.6%) of cases developed both local and systemic envenomation. Moderate local pain is the most common sign at presentation (n = 187, 36.5%). Eye pain (n = 56) and conjunctival injection (red eye) (n = 36) were frequent complaints following venom ophthalmia. Bite cases frequently presented with local pain (n = 386) and swelling (n = 310). The common systemic manifestations following Naja species bite were vomiting (n = 54) and ptosis (n = 37).

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Table 2. Diagnosis, prehospital care intervention and clinical pattern of Naja species related injuries consulted to RECS from 2020–2023.

https://doi.org/10.1371/journal.pntd.0013271.t002

Antivenoms were administered to 157 (30.7%) bite cases, with the majority were for undifferentiated Naja species cases (n = 96, 61.1%), followed by N. sumatrana (n = 35, 22.3%) and N. kaouthia (n = 26, 16.6%) (Table 3). The commonest antivenom used was Thai Red Cross Naja kaouthia monospecific antivenom (NKAV) (n = 123, 78.3%) with 75 (61.0%) patients received one dose (5 vials). The median time interval from door to receiving the first dose of antivenom (DAV) was 12 h (IQR: 5.5-14.5 h) with the maximum time interval of 23 h. Intramuscular anti-tetanus toxoid (ATT) was administered in 262 (51.2%) cases. Antibiotics was administered in 157 (30.7%) cases with Amoxicillin/clavulanate (n = 76) being the commonest. Culture and sensitivity were performed in 63 (14.0%) bite cases and the most common organism was Morganella morganii (n = 6). Complications during hospital stay were documented in 38 (8.2%) patients and mostly were due to wound infection (n = 34). Surgical intervention was conducted in 53 (11.8%) bite cases with 48 (90.6%) underwent wound debridement. Among those with systemic envenomation, the most frequent emergency resuscitation was for airway intubation and ventilation (n = 21). Two patients had cardiopulmonary resuscitation (CPR). Majority of the admission to critical care units were due to systemic envenomation (n = 8, 57.1%). Most patients were hospitalized for one day (n = 153, 29.9%) and the longest duration of hospitalization was 21 days.

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Table 3. Interventions and outcomes of Naja species related injuries consulted to RECS from 2020–2023.

https://doi.org/10.1371/journal.pntd.0013271.t003

The median length of the stay was 1 (IQR: 1–3). There is an association between the length of hospital stay with the type of envenomation and antivenom usage (S1 Table). A comparative analysis for antivenom usage and length of hospital stay (LOS) was conducted between N. kaouthia and N. sumatrana envenomation cases using the Mann-Whitney U test (S2 Table). The median total antivenom usage was five vials for both species. However, the interquartile range (IQR) was broader in N. kaouthia cases (5.00) compared to N. sumatrana (0.00), indicating greater variability in antivenom administration. Despite this, there was no statistically significant difference in the total antivenom usage between the two species (U = 406.50, p = 0.393). The LOS also showed a comparable median duration of 1 day for both species. However, N. kaouthia cases had a slightly wider IQR (1.75 days) compared to N. sumatrana (1.00 days). The Mann-Whitney U test did not reveal a statistically significant difference in LOS duration between the two groups (U = 5640.00, p = 0.615). Four deaths were documented with three cases were envenomation from undifferentiated Naja species and one N. kaouthia. Causes of death were due to septic shock, basilar artery occlusion, hypoxic ischemic encephalopathy, and respiratory failure (S3 Table). No antivenom usage, complications or death were recorded for venom ophthalmia cases. There was no significant difference in clinical pattern of injury, management, and outcome between N. kaouthia and N. sumatrana envenomation (p > 0.05) (S4 Table).

Discussion

This is the first retrospective cross-sectional study describing the demographic and clinical features of bites by Naja species in Malaysia. Previous single-centered studies in Malaysia, though limited, have also highlighted cobras as the predominant cause of venomous snakebites [20–22]. However, none specifically analyze and compare the two indigenous Naja species. The findings of this study are comparable with previous studies in Southeast Asia [17,23–25]. In this study, the frequency of N. sumatrana injuries was found to be higher compared to N. kaouthia. This may reflect geographical differences in Naja species distribution between Malaysia and Thailand. The high percentage of undifferentiated Naja species cases highlights a common challenge in snakebite management. In many instances of unidentified snakebite, the patient killed and threw away the culprit snake without taking any photographic evidence. This highlights the need to improve snake identification methods in pre-clinical settings, such as increasing the awareness among the public to take pictures of the culprit snake before going to the hospital. The use of rapid immunodiagnostic tests may not be relevant for differentiating the two Naja species as the management is the same for both. However, the clinical features of local envenomation in Naja species and syndromic approach could distinguish envenoming manifestations from the other elapid bite in Malaysia. Detailed history, examination and serial documentation of progress including the blood tests could further provide clues of the culprit snake.

Naja kaouthia is found mainly in the northern, central and the east coast region of Peninsular Malaysia while N. sumatrana were found throughout Peninsular Malaysia and East Malaysia [5,6,8]. This distribution aligns with the known geographical range of these species. According to the WHO’s Guidelines for the Management of Snakebites (2016), N. kaouthia is widely distributed across Southeast Asia, while N. sumatrana is more localized to peninsular Malaysia, southern Thailand, and parts of Indonesia [15]. Our findings suggested that N. kaouthia is also present in the states of Sarawak, Pahang, Negeri Sembilan and Johor. This finding is unusual and may suggest the possibility of the introduction of non-native species in the localities either by importation or irresponsible release (escapees). The finding of N. kaouthia in these states may not affect the clinical management.

A crucial finding is that most were non-occupational. This challenges the traditional stereotype of snakebite as a hazard confined to agricultural workers. The data suggests a more pervasive pattern of peri-domestic and recreational encounters, where human habitats (homes, gardens) and snake habitats increasingly overlap. This has direct implications for public health messaging, which must target the public with information about risks in residential areas, not just farmers in fields. Despite the inappropriate first aid practices, the public appears to understand the urgency of seeking professional medical care.

The data shows that both N. kaouthia and N. sumatrana primarily caused local envenomation, with a smaller proportion of cases involving systemic effects. This is consistent with the general envenomation profile of Asian cobras [24,26]. Venom ophthalmia appears to be associated only with N. sumatrana. This aligns with reports that described N. sumatrana as having a unique ability to “spit” venom, leading to ocular injuries [3]. However, no permanent loss of vision was reported in this study. While there was no significant difference in initial pain scores and systemic envenomation from a bite between the two species, N. kaouthia bites appeared to require more frequent wound debridement. This may suggest a higher severity of local tissue necrosis from N. kaouthia bite. This discrepancy may reflect differences in venom composition between both species [13,14,27–32].

Most envenomation cases in this study received monovalent AV, rather than polyvalent or a combination of both. The appropriate antivenoms currently in use are the Thai Red Cross NKAV and Neuropolyvalent antivenom (NPAV), NKAV is primarily used to treat N. kaouthia envenomations and has been shown to cross-neutralize the venom of N. sumatrana [27–29]. These antivenoms are associated with a low incidence of adverse effects and have reduced the fatality rate associated with envenomation by Naja species. The adverse effects mainly involve acute hypersensitivity reactions of varying severity, with these occurring more frequently than delayed hypersensitivity reactions. The primary toxic components in the Naja species venom are three-finger toxins and phospholipase A2, both of which are targeted by the Thai cobra AV. One of the three-finger toxins, alpha-neurotoxin, exhibits varying levels of abundance across different populations of Naja species from distinct geographical regions, meaning that the potency of the antivenom may vary depending on the incident location [27,31–33]. However, this discrepancy is not observed in this study.

There is a similar pattern of antivenom usage for N. kaouthia and N. sumatrana cases, with NKAV being the predominant choice. The less frequent use of NPAV reflects the clinical practices of determining the species prior to antivenom administration even for undifferentiated cobra bite. Patients diagnosed with an undifferentiated sp. bite were the most likely to receive antivenom, and they accounted for the majority of all antivenom doses administered. This suggests that when the specific species is unknown, clinicians may have a lower threshold for treatment. The selection of NKAV or NPAV may also be affected by the availability of the antivenom stocks in individual hospitals. This is reflected by some patients receiving both types of antivenom. This study identified two patients who received inappropriate antivenom resulting in one death. One patient was administered with Hemato Polyvalent Antivenom (HPAV) prior to RECS consultation. It was initially treated as unidentified snakebite due to unavailability of photographic evidence of the culprit snake. Following RECS consultation, the diagnosis was documented as N. sumatrana bite. QSMI monovalent NKAV was administered and the patient survived. In the case that resulted in death, it was diagnosed as unidentified snakebite probably from a pit viper bite and Calloselasma rhodostoma antivenom (CRAV) was administered without consulting RECS. RECS was consulted after death and the diagnosis was documented as undifferentiated Naja sp. bite envenomation.

The predominance of local over systemic manifestations is consistent with the clinical profile of Asian cobra bites described in the literature. Neurotoxicity is less prominent in Asian Naja sp. bites compared to African Naja sp, with local tissue damage being the primary concern [1]. Several studies involving Thai Naja sp. (N. kaouthia, N. sumatrana and Naja siamensis) have identified local envenomation as the most common clinical manifestation, particularly pain, swelling, and skin necrosis at the bite site [17,23–25,27,33]. Local tissue necrosis, often accompanied by pain and swelling, can occur even in the absence of neurological or cardiovascular dysfunctions [34–37]. These dermonecrosis may necessitate surgical interventions such as wound debridement, skin grafting, or, in extreme cases, amputation.

Systemic envenomation form Naja species is also associated with acute neurological dysfunction including ptosis, ophthalmoplegia, dysphagia, aphasia, hypersalivation, and, in severe cases, respiratory paralysis [10]. A study in Thailand found that most patients bitten by Naja sp. exhibited systemic neurological effects, with ptosis being the most common symptom, followed by muscle paralysis, bulbar palsy, dysphagia, and ophthalmoplegia [24]. Neurological symptoms were more frequently observed in patients bitten by the monocled cobra (N. kaouthia) compared to those bitten by undifferentiated spitting cobras (N. sumatrana and N. siamensis). N. kaouthia envenomation was more likely to require endotracheal intubation and ventilatory support than bites from spitting cobras. However, this study found that envenomation by N. kaouthia did not result in significantly more systemic effects compared to N. sumatrana (p > 0.05).

The use of antibiotics in some of the cases in this study is noteworthy. While this practice aims to prevent secondary infections, it contrasts with some recent recommendations that argued against routine antibiotic prophylaxis in snakebites, suggesting it should be reserved for cases with signs of infection [15,19,38–41]. Local effects of snakebite are often mistaken for infectious changes and can contribute to unsupported provision of antibiotics, therefore warrants careful considerations. There is no evidence supporting prophylactic antibiotics in the acute phase of clinical management unless there is evidence of secondary infection or a history of manipulation of the wound or environmental contamination [10,15,19]. The findings highlight the need for adherence to the evidence-based snakebite management guidelines in Malaysia.

The generally favorable outcomes observed in this study, with low mortality are encouraging. The comparative analysis between the length of hospital stay with antivenom usage suggests that the envenomation by both species resulted in similar patterns of antivenom administration and hospitalization duration, with no significant differences detected in these clinical outcomes. These results compare favorably with past data [22]. A study in Thailand reported a low mortality rate of 1.7%, all of which occurred in patients with N. kaouthia bites with varying durations of hospitalization [24]. The low mortality rate in Malaysia and Thailand reflects advancements in healthcare quality, improved support for snakebite management, and the availability and supply of appropriate antivenom [41–43]. Critically, the deaths were attributed to secondary complications that arose during hospitalization, not to untreatable, acute venom toxicity.

Complications were observed in both N. kaouthia and N. sumatrana cases and was primarily due to wound infection. Necrotizing fasciitis occurred at a higher percentage in N. kaouthia cases. This rate is higher than that reported in a study from Taiwan, which documented a 3.8% complication rate for Naja atra bites [44]. The difference could be due to variations in the snake species, environmental factors, patient characteristics, or healthcare practices. In Thailand, surgical interventions such as amputation, debridement, and skin grafting were more frequently performed in cases involving N. kaouthia envenomation [24]. Most patients with N. kaouthia bites in Thailand were asymptomatic or mildly symptomatic and were discharged after 3 to 4 days [17]. Hospitalization was significantly prolonged for patients with tissue necrosis, ranging from 20 to 29 days. These findings suggest a need to improve wound care practices. The observed discrepancies highlight the importance of further research to develop a comprehensive understanding of the differing clinical outcomes between Naja kaouthia and Naja sumatrana envenomations in Malaysia.

There appears to be a significant variability in the Bite-to-Door (BTD) and Door-to-Antivenom (DTA) administration time intervals. A DTA paradox. Bite-to-door time shows that most patients seek early medical care, often before clear indications for antivenom. However, a few patients had experienced extreme delays in reaching medical care. These were likely due to geographical barriers, limited access to emergency services, or delays in seeking help. Similarly, DTA times may highlight prolonged and inconsistent delays. However, since many patients arrived early at an emergency department, signs of systemic envenomation may not yet have been apparent. The 12-hour gap represents the necessary period of close serial observation during which the patient’s progression is monitored to determine if the envenomation is severe enough to warrant AV, thereby avoiding its overuse and the risk of adverse reactions. Close serial observation of the trends in proximal progression of swelling, pain score, expansion of dermonecrosis and blood tests should become the standard practice when assessing indications for AV.

RECS management strategies emphasize accurate snake species identification, close serial observation, effective pain management, judicious use of antibiotics and appropriate and timely use of antivenom. This aligns with the current national guidelines [19]. The WHO (SEARO) recommends a similar approach, emphasizing the importance of early antivenom administration in cases of systemic envenoming or severe and progressive local effects [15]. The findings of this study highlight the need to increase public awareness on appropriate health seeking behavior, optimizing emergency response systems for faster patient transportation and streamlining hospital protocols for timely antivenom administration. These will ultimately improve patient outcomes and reduce mortality.

Conclusion

Naja species envenomation in Malaysia is a manageable condition with low mortality but, carries a significant risk of local tissue damage. Antivenom is judiciously administered, while surgery is needed to facilitate wound healing. This study highlights the importance of species-specific research, offering essential data for public health strategies, clinical management, and future research on snake related injuries in Malaysia. The Thai Red Cross cobra antivenom effectiveness in both species supports current antivenom strategies. Despite favorable outcomes, complication rates suggest areas for improvement in wound care and infection prevention by examining risk factors for complications and exploring interventions to reduce them in the future.

Supporting information

Acknowledgments

Gratitude is extended to the entire team at Remote Envenomation Consultation Services (RECS) for their dedication to patient care and meticulous data collection. Acknowledgement is also given to Nur Hazwanie Abd Halim and Nurfarhana Hizan Hijas from Malaysia Biodiversity Information System (MyBIS); Nurul Saadah Ahmad and Abdul Karim Mustafa from the Department of Emergency Medicine, UKM; Khairul Hazdi Yusof from the Risk Management Unit, HCTM. The authors also acknowledge Putra Jeffri Daniel Othman, Dr. Nabil Muhammad Al Kuddoos and Muhamad Khaidir Arif Che Mat.