A case of rotenone poisoning from ingesting Derris trifoliata Lour. (Tuba fruit/pod) in Malaysia.

Derris trifoliata is mainly found in mangrove area in tropical regions and the plant extract is traditionally used for fishing by poisoning. This is the first case report of rotenone poisoning in a child from ingesting Derris trifoliata seed. The child developed altered consciousness, vomiting, hypotension, metabolic acidosis, and acute kidney injury. Species identification of this case requires the collaborative efforts of various agencies. She survived from the poisoning with no neurological sequelae.

Frequency, geographical distribution and outcomes of pit viper bites in Malaysia consulted to Remote Envenomation Consultancy Services (RECS) from 2017 to 2020.

Not all pit viper species are present in every state of Malaysia and their distribution varies according to altitude. There is limited information on pit viper bite incidence and its geographical distribution. This was a cross-sectional study of confirmed pit viper bite cases referred to Remote Envenomation Consultancy Services (RECS) from January 2017 to December 2020. Data was collected following the approval of institutional research ethics committee. Universal sampling methods were used. Confirmed pit viper bite cases in each state, geographical location and the antivenom used were reported. A total of 523 confirmed pit viper bite injuries occurred over the 4-year study period. The majority were Malaysians, male and young adults. Most were non-occupational related (83.9%) and involved the upper limbs (46.8%). The commonest pit viper species involved was Trimeresurus purpureomaculatus (23.7%). Green pit viper antivenom (GPAV) was the most frequent antivenom used (n = 51) with the majority of patients requiring only one dose (3 vials). This study provides a better appreciation of indigenous pit viper species distribution for each state and reflects the requirement of appropriate antivenom to be stocked in each state or district hospital.

Application of Sonographic Assessments of the Rate of Proximal Progression to Monitor Protobothrops mucrosquamatus Bite-Related Local Envenomation: A Prospective Observational Study.

Patients bitten by Protobothrops mucrosquamatus typically experience significant pain, substantial swelling, and potentially blister formation. The appropriate dosage and efficacy of FHAV for alleviating local tissue injury remain uncertain. Between 2017 and 2022, 29 snakebite patients were identified as being bitten by P. mucrosquamatus. These patients underwent point-of-care ultrasound (POCUS) assessments at hourly intervals to measure the extent of edema and evaluate the rate of proximal progression (RPP, cm/hour). Based on Blaylock's classification, seven patients (24%) were classified as Group I (minimal), while 22 (76%) were classified as Group II (mild to severe). In comparison to Group I patients, Group II patients received more FHAV (median of 9.5 vials vs. two vials, p-value < 0.0001) and experienced longer median complete remission times (10 days vs. 2 days, p-value < 0.001). We divided the Group II patients into two subgroups based on their clinical management. Clinicians opted not to administer antivenom treatment to patients in Group IIA if their RPP decelerated. In contrast, for patients in Group IIB, clinicians increased the volume of antivenom in the hope of reducing the severity of swelling or blister formation. Patients in Group IIB received a significantly higher median volume of antivenom (12 vials vs. six vials; p-value < 0.001) than those in Group IIA. However, there was no significant difference in outcomes (disposition, wound necrosis, and complete remission times) between subgroups IIA and IIB. Our study found that FHAV does not appear to prevent local tissue injuries, such as swelling progression and blister formation, immediately after administration. When administering FHAV to patients bitten by P. mucrosquamatus, the deceleration of RPP may serve as an objective parameter to help clinicians decide whether to withhold FHAV administration.

Managing an Unidentified Jellyfish Sting with Mixed Envenomation Syndrome at a Noncoastal Hospital: Is This a New Form of Jellyfish Envenomation?

Jellyfish stings are the most common cause of marine envenomation in humans. Various species of box jellyfish have been identified around Penang Island, Malaysia, and these include multitentacled and four-tentacled box jellyfish (class Cubozoa). The typical syndrome following envenomation from these jellyfish has been poorly documented, posing a greater challenge when managing an unidentified jellyfish sting from Penang Island. We report a case of a 32-y-old man from Penang Island who was stung by an unidentified jellyfish while walking into the sea. The patient reported that he felt an immediate and severe electric current‒like pain over both thighs, left flank, and left forearm, followed by chest discomfort and breathlessness. Vinegar was applied over the affected areas, and he was rushed to a hospital, where he was treated with analgesia, steroids, and antihistamine. He refused hospitalization and was discharged against medical advice. He then presented to a noncoastal hospital 377 km away in Kuala Lumpur on the following day with severe pain over the affected sites as well as chest discomfort, shortness of breath, and abdominal cramps. The electrocardiograph demonstrated features of Wolff-Parkinson-White. Serial blood test results showed elevated creatine kinase but normal troponin I levels. The patient was managed symptomatically over a period of 4 d and was discharged with cardiology follow-up. Appropriate health-seeking behavior needs to be emphasized. This case report provides an opportunity to document the signs and symptoms of envenomation from possibly an undescribed jellyfish species near the coastal waters of Penang Island.

Frequency, clinical characteristics and outcomes of Tropidolaemus species bite envenomations in Malaysia.

Pit vipers from the genus Tropidolaemus are identified as one of the common causes of snake bite from venomous species in Malaysia. All Tropidolaemus species bite cases referred to the Remote Envenomation Consultation Services (RECS) between 2015-2021 were included. A total of 4,718 snake-related injuries cases consulted to RECS with 310 (6.6%) involved Tropidolaemus species; of these 190 (61.3%) were T. subannulatus and 120 (38.7%) T. wagleri. All the T. subannulatus cases occurred in Sabah and Sarawak while all cases of T. wagleri occurred in Peninsular Malaysia. The majority of patients were male (74.8%) and adults between 18-59 years old (61.2%). The upper limb (56.6%) was the most frequent anatomical region involved. Most cases were non-occupationally related (75.4%). Bites from both species caused local pain (77.1%) and swelling (27.2%). Most patients complained of mild pain (48.0%). Paracetamol (40.0%) was the most common analgesic prescribed. Antivenom was not indicated in all cases. Two patients were given antivenom inappropriately before RECS consultation. Most patients (54.7%) needed hospital observation for less than 24 hours. No deaths occurred in the group studied.

A case of fatal envenomation by a captive puff adder (Bitis arietans) in Malaysia.

The Puff Adder (Bitis arietans) is a viper native to Africa and the Middle East. Envenomation by this species often requires the administration of appropriate antivenom in order to achieve a favorable outcome. A patient was bitten in both hands by a captive B. arietans presented to a teaching hospital in Malaysia. The patient developed painful progressive swelling on both limbs that extended to the chest, hypotension, hypokalemia with worsening anemia, thrombocytopenia, coagulopathy, and severe metabolic acidosis. The patient was managed supportively while waiting for the appropriate antivenom, Antivipmyn-Africa, from the Singapore Zoo. The patient developed cardiorespiratory arrest twice and did not recover from the second. The patient was pronounced dead 23 hours post-incident. The local unavailability of the appropriate antivenom may be the most important factor that contributed to the patient's death. There is also a need to amend the Malaysian Wildlife Act in order to prevent such cases from recurring.

Experience of using expired lyophilized snake antivenom during a medical emergency situation in Lao People's Democratic Republic--A possible untapped resource to tackle antivenom shortage in Southeast Asia.

OBJECTIVES: To evaluate the safety and efficacy of expired lyophilized snake antivenom of Thai origin during a medical emergency in 2020/2021 in Lao People's Democratic Republic. METHODS: Observational case series of patients with potentially life-threatening envenoming who consented to the administration of expired antivenom between August 2020 and May 2022. RESULTS: A total of 31 patients received the expired antivenom. Malayan pit vipers (Calloselasma rhodostoma) were responsible for 26 (84%) cases and green pit vipers (Trimeresurus species) for two cases (6%). In three patients (10%) the responsible snake could not be identified. Of these, two presented with signs of neurotoxicity and one with coagulopathy. A total of 124 vials of expired antivenom were administered. Fifty-nine vials had expired 2-18 months earlier, 56 vials 19-36 months and nine vials 37-60 months before. Adverse effects of variable severity were observed in seven (23%) patients. All 31 patients fully recovered from systemic envenoming. CONCLUSIONS: Under closely controlled conditions and monitoring the use of expired snake antivenom proved to be effective and safe. Discarding this precious medication is an unnecessary waste, and it could be a valuable resource in ameliorating the current shortage of antivenom. Emergency use authorization granted by health authorities and preclinical testing of expired antivenoms could provide the support and legal basis for such an approach.

Potential economic and clinical implications of improving access to snake antivenom in five ASEAN countries: A cost-effectiveness analysis.

BACKGROUND: Despite domestic production of antivenoms in the Association of Southeast Asian Nations (ASEAN) countries, not all victims with snakebite envenomings indicated for antivenom received the appropriate or adequate effective dose of antivenom due to insufficient supply and inadequate access to antivenoms. We aimed to conduct a cost-effectiveness analysis to project the potential economic and clinical impact of improving access to antivenoms when all snakebite envenomings in ASEAN countries were hypothetically treated with geographically appropriate antivenoms. METHODOLOGY: Using a decision analytic model with input parameters from published literature, local data, and expert opinion, we projected the impact of "full access" (100%) to antivenom, compared to "current access" in five most impacted ASEAN countries, including Indonesia (10%), Philippines (26%), Vietnam (37%), Lao PDR (4%), and Myanmar (64%), from a societal perspective with a lifetime time horizon. Sensitivity analyses were performed. PRINCIPAL FINDINGS: In base-case analyses, full access compared to current access to snake antivenom in the five countries resulted in a total of 9,362 deaths averted (-59%), 230,075 disability-adjusted life years (DALYs) averted (-59%), and cost savings of 1.3 billion USD (-53%). Incremental cost-effectiveness ratios (ICERs) of improving access to antivenom found higher outcomes but lower costs in all countries. Probabilistic sensitivity analyses of 1,000 iterations found that 98.1-100% of ICERs were cost-saving. CONCLUSION/SIGNIFICANCE: Improving access to snake antivenom will result in cost-saving for ASEAN countries. Our findings emphasized the importance of further strengthening regional cooperation, investment, and funding to improve the situation of snakebite victims in ASEAN countries.

In Vitro neurotoxicity and myotoxicity of Malaysian Naja sumatrana and Naja kaouthia venoms: Neutralization by monovalent and Neuro Polyvalent Antivenoms from Thailand.

Naja sumatrana and Naja kaouthia are medically important elapids species found in Southeast Asia. Snake bite envenoming caused by these species may lead to morbidity or mortality if not treated with the appropriate antivenom. In this study, the in vitro neurotoxic and myotoxic effects N. sumatrana and N. kaouthia venoms from Malaysian specimens were assessed and compared. In addition, the neutralizing capability of Cobra Antivenom (CAV), King Cobra Antivenom (KCAV) and Neuro Polyvalent Antivenom (NPAV) from Thailand were compared. Both venoms produced concentration-dependent neurotoxic and myotoxic effects in the chick biventer cervicis nerve-muscle preparation. Based on the time to cause 90% inhibition of twitches (i.e. t90) N. kaouthia venom displayed more potent neurotoxic and myotoxic effects than N. sumatrana venom. All three of the antivenoms significantly attenuated venom-induced twitch reduction of indirectly stimulated tissues when added prior to venom. When added after N. sumatrana venom, at the t90 time point, CAV and NPAV partially restored the twitch height but has no significant effect on the reduction in twitch height caused by N. kaouthia venom. The addition of KCAV, at the t90 time point, did not reverse the attenuation of indirectly stimulated twitches caused by either venom. In addition, none of the antivenoms, when added prior to venom, prevented attenuation of directly stimulated twitches. Differences in the capability of antivenoms, especially NPAV and CAV, to reverse neurotoxicity and myotoxicity indicate that there is a need to isolate and characterize neurotoxins and myotoxins from Malaysian N. kaouthia and N. sumatrana venoms to improve neutralization capability of the antivenoms.

Estimating economic and disease burden of snakebite in ASEAN countries using a decision analytic model.

BACKGROUND: Understanding the burden of snakebite is crucial for developing evidence-informed strategies to pursue the goal set by the World Health Organization to halve morbidity and mortality of snakebite by 2030. However, there was no such information in the Association of Southeast Asian Nations (ASEAN) countries. METHODOLOGY: A decision analytic model was developed to estimate annual burden of snakebite in seven countries, including Malaysia, Thailand, Indonesia, Philippines, Vietnam, Lao PDR, and Myanmar. Country-specific input parameters were sought from published literature, country's Ministry of Health, local data, and expert opinion. Economic burden was estimated from the societal perspective. Costs were expressed in 2019 US Dollars (USD). Disease burden was estimated as disability-adjusted life years (DALYs). Probabilistic sensitivity analysis was performed to estimate a 95% credible interval (CrI). PRINCIPAL FINDINGS: We estimated that annually there were 242,648 snakebite victims (95%CrI 209,810-291,023) of which 15,909 (95%CrI 7,592-33,949) were dead and 954 (95%CrI 383-1,797) were amputated. We estimated that 161,835 snakebite victims (69% of victims who were indicated for antivenom treatment) were not treated with antivenom. Annual disease burden of snakebite was estimated at 391,979 DALYs (95%CrI 187,261-836,559 DALYs) with total costs of 2.5 billion USD (95%CrI 1.2-5.4 billion USD) that were equivalent to 0.09% (95%CrI 0.04-0.20%) of the region's gross domestic product. >95% of the estimated burdens were attributed to premature deaths. CONCLUSION/SIGNIFICANCE: The estimated high burden of snakebite in ASEAN was demonstrated despite the availability of domestically produced antivenoms. Most burdens were attributed to premature deaths from snakebite envenoming which suggested that the remarkably high burden of snakebite could be averted. We emphasized the importance of funding research to perform a comprehensive data collection on epidemiological and economic burden of snakebite to eventually reveal the true burden of snakebite in ASEAN and inform development of strategies to tackle the problem of snakebite.

Situation of snakebite, antivenom market and access to antivenoms in ASEAN countries.

INTRODUCTION: Snakebite envenoming is a neglected tropical disease posing public health challenges globally. The Association of Southeast Asian Nations (ASEAN) countries are among the tropical regions with disproportionately high incidence of snakebite. Hence, this study aimed to review the situation of snakebite, antivenom market and access to antivenoms in ASEAN. METHODS: This mixed-methods study included comprehensive literature review and in-depth interviews with key informants to assess the situation of management system of snakebite, antivenom market and access to antivenoms in seven ASEAN countries, including Malaysia, Thailand, Indonesia, Philippines, Vietnam, Lao PDR and Myanmar. Data were analysed by a framework method. RESULTS: ASEAN have developed various strategies to improve outcomes of snakebite victims. Five domestic antivenom manufacturers in the region produce up to 288 375 vials of antivenoms annually with the value of US$13 058 053 million which could treat 42 213 snakebite victims. However, there remain challenges to be addressed especially the lack of snakebite-related informatics system, inadequate antivenoms at the healthcare facilities and when the majority of snakebite victims seek traditional healers instead of conventional treatment. CONCLUSION: Improving the situation of snakebite and antivenom is not only about the availability of antivenom, but the whole landscape of surrounding management and supporting system. The assessment of the situation of snakebite and antivenom is crucial for countries or regions where snakebites are prevalent to recognise their current standpoint to inform the development of strategies to achieve the goal set by the WHO of halving the global burden of snakebite by 2030.

Estimation of local incidence of jellyfish envenomation in developed marine coastal areas and large populated island on the western coast of Peninsular Malaysia using case surveillance of government health facilities in Manjung, Perak and Langkawi Island.

BACKGROUND: Jellyfish stings are one of the commonest causes of marine animal related injuries in human. Despite mostly being harmless, box jellyfish species can cause major stings with fatalities or systemic envenoming symptoms. There are 15-20 species identified to be life-threatening. There are few reported cases that suggest the presence of deadly box jellyfish in the Malaysian coast. However, numbers of stings around Malaysia are still under reported. MATERIALS AND METHODS: This observational study was conducted in Manjung, Perak and Langkawi Island to look at the pattern and incidence of jellyfish stings which occur within 1 year. RESULTS: There were 45 sting incidents reported with the highest number of cases occurred in December and February. Cases mainly involved young adults aged 10 to 29 years old. The most common clinical symptom that presented was sudden and persistent pain. Vinegar was applied as first aid in 53.3% of reported stings. All patients were treated symptomatically and discharged well. Stings occurred at mean sea surface temperature of 29.38°C and the wind speed of 7.6 knots. All cases were mild and did not require antivenom. CONCLUSIONS: The study showed that the occurrence of jellyfish stings are affected by weather conditions. Jellyfish stings occur seasonally, thus making it predictable and easily preventable with public awareness, early first aid application and use of jellyfish nets.

Health Anxiety and Its Correlations with Self-Perceived Risk and Attitude on COVID-19 among Malaysian Healthcare Workers during the Pandemic.

Healthcare workers (HCW) are exposed to health-related anxiety in times of pandemic as they are considered to have a high risk of being infected whilst being the vital workforce to manage the outbreak. This study determined the factors that influence health anxiety and its extent in correlations with perceived risk, knowledge, attitude, and practice of HCW. A cross-sectional online survey was conducted on a total of 709 HCW from both public and private healthcare facilities who completed a set of questionnaires on sociodemographic data, knowledge, attitude, and practice of HCW on COVID-19, and health anxiety traits assessed using the short version Health Anxiety Inventory (HAI). Multiple linear regression (adjusted R2 = 0.06) revealed respondents with higher perceived risk for COVID-19 significantly predicted higher HAI scores (beta 1.281, p < 0.001, 95%, CI: 0.64, 1.92), and those with a higher cautious attitude towards COVID-19 significantly predicted higher HAI scores (beta 0.686, p < 0.001, 95%CI: 0.35, 1.02). Healthcare workers' perceived risk and cautious attitude towards COVID-19 might be potentially influenced by management of the sources and approaches to the dissemination of information of the pandemic. The implementation of certain measures that minimize the infection risk and its related anxiety is important to preserve both their physical and psychological wellbeing.

The role of a point-of-care ultrasound protocol in facilitating clinical decisions for snakebite envenomation in Taiwan: a pilot study.

BACKGROUND: The incidence of acute compartment syndrome (ACS) following snakebite envenomation may be seriously overestimated in Taiwan. Snakebite-induced ACS is difficult to determine solely by clinical examination. Snakebite patients previously underwent surgical intervention based on speculation and general clinical examinations suggesting ACS presentations instead of direct intracompartmental pressure (IP) measurement prior to fasciotomy. Point-of-care ultrasound (POCUS) is a relatively widely available noninvasive tool. This study aimed to evaluate snakebite-envenomated patients for the presence of subcutaneous edema and diastolic retrograde arterial flow (DRAF). MATERIALS AND METHODS: Snakebite patients were prospectively recruited between 2017 and 2019. All patients were examined with POCUS to locate edema and directly visualize and measure the arterial flow in the compressed artery. The presence of DRAF in the compressed artery is suggestive of ACS development because when compartment space restriction occurs, increased retrograde arterial flow is observed in the artery. RESULTS: Twenty-seven snakebite patients were analyzed. Seventeen patients (63%) were bitten by Crotalinae snakes, seven (26%) by Colubridae, one (4%) by Elapidae, and two (7%) had unidentified snakebites. All Crotalinae bit patients received antivenom, had subcutaneous edema and lacked DRAF in a POCUS examination series. DISCUSSION: POCUS facilitates clinical decisions for snakebite envenomation. We also highlighted that the anatomic site of the snakebite is an important factor affecting the prognosis of the wounds. There were limitations of this study, including a small number of patients and no comparison with the generally accepted invasive evaluation for ACS. CONCLUSIONS: We are unable to state that POCUS is a valid surrogate measurement of ACS from this study but see this as a starting point to develop further research in this area. Further study will be needed to better define the utility of POCUS in patients envenomated by snakes throughout the world.

Global systematic review of cost of illness and economic evaluation studies associated with snakebite.

BACKGROUND: Snakebite envenoming, a high priority Neglected Tropical Disease categorized by the World Health Organization (WHO), has been considered as a poverty-related disease that requires greater global awareness and collaboration to establish strategies that effectively decrease economic burdens. This prompts the need for a comprehensive review of the global literature that summarizes the global economic burden and a description of methodology details and their variation. This study aimed to systematically identify studies on cost of illness and economic evaluation associated with snakebites, summarize study findings, and evaluate their methods to provide recommendations for future studies. METHODS: We searched PubMed, EMBASE, Cochrane library, and Econlit for articles published from inception to 31 July 2019. Original articles reporting costs or full economic evaluation related with snakebites were included. The methods and reporting quality were assessed. Costs were presented in US dollars (US$) in 2018. RESULTS: Twenty-three cost of illness studies and three economic evaluation studies related to snakebites were included. Majority of studies (18/23, 78.26%) were conducted in Low- and Middle-income countries. Most cost of illness studies (82.61%) were done using hospital-based data of snakebite patients. While, four studies (17.39%) estimated costs of snakebites in communities. Five studies (21.74%) used societal perspective estimating both direct and indirect costs. Only one study (4.35%) undertook incidence-based approach to estimate lifetime costs. Only three studies (13.04%) estimated annual national economic burdens of snakebite which varied drastically from US$126 319 in Burkina Faso to US$13 802 550 in Sri Lanka. Quality of the cost of illness studies were varied and substantially under-reported. All three economic evaluation studies were cost-effectiveness analysis using decision tree model. Two of them assessed cost-effectiveness of having full access to antivenom and reported cost-effective findings. CONCLUSIONS: Economic burdens of snakebite were underestimated and not extensively studied. To accurately capture the economic burdens of snakebites at both the global and local level, hospital data should be collected along with community survey and economic burdens of snakebites should be estimated both in short-term and long-term period to incorporate the lifetime costs and productivity loss due to premature death, disability, and consequences of snakebites.

Isolated Pancreatic Tail Injury in Paediatrics; A Case Report and Literature Review.

Pancreatic injury in paediatrics is a rare condition and can be difficult to diagnose. The diagnostic challenge is due to its symptom of vague abdominal pain which usually results in late presentation. Elevated biochemical markers such as amylase and lipase can aid in the evaluation of pancreatic injury, however, it is not specific and is only evident after several hours of trauma. Ultrasound is commonly used as a primary modality to evaluate abdominal organ injuries, but its role in detecting pancreatic injury is limited due to low sensitivity. High index of suspicion is needed to avoid undiagnosed pancreatic injury which could be lethal to children. We herein report a case of delayed presentation of isolated pancreatic tail injury in a child who was sufficiently diagnosed with ultrasound and treated conservatively. Proper initial assessment and diagnosis will allow appropriate management of pancreatic injury. Conservative management should include serial imaging to look at the evolution of pancreatic injury and detect complications such as pseudocyst or abscess formation.

Geographical variations in king cobra (Ophiophagus hannah) venom from Thailand, Malaysia, Indonesia and China: On venom lethality, antivenom immunoreactivity and in vivo neutralization.

The wide distribution of king cobra (Ophiophagus hannah), a medically important venomous snake in Asia could be associated with geographical variation in the toxicity and antigenicity of the venom. This study investigated the lethality of king cobra venoms (KCV) from four geographical locales (Malaysia, Thailand, Indonesia, China), and the immunological binding as well as in vivo neutralization activities of three antivenom products (Thai Ophiophagus hannah monovalent antivenom, OHMAV; Indonesian Serum Anti Bisa Ular, SABU; Chinese Naja atra monovalent antivenom, NAMAV) toward the venoms. The Indonesian and Chinese KCV were more lethal (median lethal dose, LD50 ~0.5 µg/g) than those from Malaysia and Thailand (LD50 ~1.0 µg/g). The antivenoms, composed of F(ab)'2, were variably immunoreactive toward the KCV from all locales, with OHMAV exhibited the highest immunological binding activity. In mice, OHMAV neutralized the neurotoxic lethality of Thai KCV most effectively (normalized potency = 118 mg venom neutralized per g antivenom) followed by Malaysian, Indonesian and Chinese KCV. In comparison, the hetero-specific SABU was remarkably less potent by at least 6 to10 folds, whereas NAMAV appeared to be non-effective. The finding supports that a specific king cobra antivenom is needed for the effective treatment of king cobra envenomation in each region.

Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom.

Trimeresurus nebularis is a montane pit viper that causes bites and envenomation to various communities in the central highland region of Malaysia, in particular Cameron's Highlands. To unravel the venom composition of this species, the venom proteins were digested by trypsin and subjected to nano-liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomic profiling. Snake venom metalloproteinases (SVMP) dominated the venom proteome by 48.42% of total venom proteins, with a characteristic distribution of P-III: P-II classes in a ratio of 2:1, while P-I class was undetected. Snaclecs constituted the second most venomous protein family (19.43%), followed by snake venom serine proteases (SVSP, 14.27%), phospholipases A2 (5.40%), disintegrins (5.26%) and minor proteins including cysteine-rich secretory proteins, L-amino acid oxidases, phosphodiesterases, 5'-nucleotidases. The venomic profile correlates with local (painful progressive edema) and systemic (hemorrhage, coagulopathy, thrombocytopenia) manifestation of T. nebularis envenoming. As specific antivenom is unavailable for T. nebularis, the hetero-specific Thai Green Pit viper Monovalent Antivenom (GPVAV) was examined for immunological cross-reactivity. GPVAV exhibited good immunoreactivity to T. nebularis venom and the antivenom effectively cross-neutralized the hemotoxic and lethal effects of T. nebularis (lethality neutralizing potency = 1.6 mg venom per mL antivenom). The findings supported GPVAV use in treating T. nebularis envenoming.

Unlocking the secrets of banded coral snake (Calliophis intestinalis, Malaysia): A venom with proteome novelty, low toxicity and distinct antigenicity.

The Asiatic coral snakes are basal in the phylogeny of coral snakes. Although envenoming by the Asiatic coral snakes is rarely fatal, little is known about their venom properties and variability from the American coral snakes. Integrating reverse-phase high performance liquid chromatography and nano-liquid chromatography-tandem mass spectrometry, we showed that the venom proteome of the Malaysian banded or striped coral snake (Calliophis intestinalis) was composed of mainly phospholipases A2 (PLA2, 43.4%) and three-finger toxins (3FTx, 20.1%). Within 3FTx, the cytotoxins or cardiotoxins (CTX) dominated while the neurotoxins' content was much lower. Its subproteomic details contrasted with the 3FTx profile of most Micrurus sp., illustrating a unique dichotomy of venom phenotype between the Old and the New World coral snakes. Calliophis intestinalis venom proteome was correlated with measured enzymatic activities, and in vivo it was myotoxic but non-lethal to mice, frogs and geckos at high doses (5-10 µg/g). The venom contains species-specific toxins with distinct sequences and antigenicity, and the antibodies raised against PLA2 and CTX of other elapids showed poor binding toward its venom antigens. The unique venom proteome of C. intestinalis unveiled a repertoire of novel toxins, and the toxicity test supported the need for post-bite monitoring of myotoxic complication. SIGNIFICANCE: Malaysian banded or striped coral snake (Calliophis intestinalis) has a cytotoxin (CTX)-predominating venom proteome, a characteristic shared by its congener, the Malayan blue coral snake (Calliophis bivirgata). With little neurotoxins (NTX), it illustrates a CTX/NTX dichotomy of venom phenotype between the Old World and the New World coral snakes. The low toxicity of the venom imply that C. intestinalis bite envenoming can be managed via symptomatic relief of the mild to moderate pain with appropriate analgesia. Systemically, the serum creatine kinase level of patients should be monitored serially for potential complication of myotoxicity. The distinct antigenicity of the venom proteins implies that the empirical use of heterologous antivenom is mostly inappropriate and not recommended.

Cross reactivity and lethality neutralization of venoms of Indonesian Trimeresurus complex species by Thai Green Pit Viper Antivenom.

Arboreal pit vipers of the Trimeresurus complex group are medically important species in Indonesia (west of Wallace's line), but there is no specific antivenom produced in the country for treating related envenomation. Instead, the exiting trivalent Indonesian antivenom, Biosave® Serum Anti Bisa Ular (SABU, indicated for envenoming by Malayan pit viper, Javan spitting cobra and banded krait) is often misused to treat Trimeresus envenoming resulting in poor therapeutic outcome. Here, we investigated the cross-reactivity and neutralization capability of Thai Green Pit Viper Antivenom (GPVAV) against the venoms of four Indonesian Trimeresurus species. Consistently, the venoms of Trimeresurus (Trimeresurus) insularis, Trimeresurus (Trimeresurus) purpureomaculatus, Trimeresurus (Parias) hageni and Trimeresurus (Craspedocephalus) puniceus of Indonesia showed stronger immunoreactivity on ELISA to GPVAV than to Biosave®. The findings correlated with in vivo neutralization results, whereby GPVAV was far more effective than Biosave® in cross-neutralizing the lethality of the venoms by a potency of at least 13 to 80 times higher. The efficacy of GPVAV is partly attributable to its cross-neutralization of the procoagulant effect of the venoms, thereby mitigating the progression of venom-induced consumptive coagulopathy. The paraspecific effectiveness of GPVAV against Trimeresurus species envenoming in Indonesia await further clinical investigation.