In Southeast Asia, envenoming resulting from cobra snakebites is an important public health issue in many regions, and antivenom therapy is the standard treatment for the snakebite. Because these cobras share a close evolutionary history, the amino acid sequences of major venom components in different snakes are very similar. Therefore, either monovalent or polyvalent antivenoms may offer paraspecific protection against envenomation of humans by several different snakes. In Taiwan, a bivalent antivenom—freeze-dried neurotoxic antivenom (FNAV)—against Bungarus multicinctus and Naja atra is available. However, whether this antivenom is also capable of neutralizing the venom of other species of snakes is not known. Here, to expand the clinical application of Taiwanese FNAV, we used an animal model to evaluate the neutralizing ability of FNAV against the venoms of three common snakes in Southeast Asia, including two ‘true’ cobras Naja kaouthia (Thailand) and Naja siamensis (Thailand), and the king cobra Ophiophagus hannah (Indonesia). We further applied mass spectrometry (MS)-based proteomic techniques to characterize venom proteomes and identify FNAV-recognizable antigens in the venoms of these Asian snakes. Neutralization assays in a mouse model showed that FNAV effectively neutralized the lethality of N. kaouthia and N. siamensis venoms, but not O. hannah venom. MS-based venom protein identification results further revealed that FNAV strongly recognized three-finger toxin and phospholipase A2, the major protein components of N. kaouthia and N. siamensis venoms. The characterization of venom proteomes and identification of FNAV-recognizable venom antigens may help researchers to further develop more effective antivenom designed to block the toxicity of dominant toxic proteins, with the ultimate goal of achieving broadly therapeutic effects against these cobra snakebites. Cobra envenomation is a public health issue in Southeast Asia. Currently, antivenom therapy is the standard treatment for snakebite. However, antivenoms are not available in many rural countries and communities or have only limited effectiveness. Taiwan has wealth of experience in producing antivenoms, including the bivalent freeze-dried neurotoxic antivenom (FNAV), which is raised against venom proteins from Bungarus multicinctus and Naja atra. Our results showed that FNAV effectively neutralized the lethality of Naja kaouthia(Thailand) and Naja siamensis (Thailand) venoms, but not Ophiophagus hannah (Indonesia) venom, in an animal model. We further characterized the venom proteome profiles of the four cobras and identified three abundant proteins—neurotoxin, cytotoxin and phospholipase A2—in the venom of N. atra, N. kaouthia and N. siamensisas the major antigens recognized by FNAV. In contrast, we found that β-cardiotoxin and phospholipase A2, common toxin proteins in all king cobra venom samples, are weakly or not recognized by FNAV. Our data provide evidence suggesting the potential use of Taiwan’s FNAV to treat envenomation by other cobra species (N. kaouthia and N. siamensis) in Southeast Asia. Moreover, our findings support the previous recommendation and current experimental approach that major cobra toxins are used as antigens to generate more efficient antivenoms than those currently available.

Background: Although the outcomes of caustic ingestion differ between children and adults, it is unclear whether such outcomes differ among adults as a function of their age. This retrospective study was performed to ascertain whether the clinical outcomes of caustic ingestion differ significantly between elderly and non-elderly adults. Methods: Medical records of patients hospitalized for caustic ingestion between June 1999 and July 2009 were reviewed retrospectively. Three hundred eighty nine patients between the ages of 17 and 107 years were divided into two groups: non-elderly (< 65 years) and elderly (≥ 65 years). Mucosal damage was graded using esophagogastroduodenoscopy (EGD). Parameters examined in this study included gender, intent of ingestion, substance ingested, systemic and gastrointestinal complications, psychological and systemic comorbidities, severity of mucosal injury, and time to expiration. Results: The incidence of psychological comorbidities was higher for the non-elderly group. By contrast, the incidence of systemic comorbidities, the grade of severity of mucosal damage, and the incidence of systemic complications were higher for the elderly group. The percentages of ICU admissions and deaths in the ICU were higher and the cumulative survival rate was lower for the elderly group. Elderly subjects, those with systemic complications had the greatest mortality risk due to caustic ingestion. Conclusions: Caustic ingestion by subjects ≥65 years of age is associated with poorer clinical outcomes as compared to subjects < 65 years of age; elderly subjects with systemic complications have the poorest clinical outcomes. The severity of gastrointestinal tract injury appears to have no impact on the survival of elderly subjects.

Snakebites from Taiwan habus (Protobothrops mucrosquamatus) and green bamboo vipers (Viridovipera stejnegeri) account for two-thirds of all venomous snakebites in Taiwan. While there has been ongoing optimization of antivenin therapy, the proper management of superimposed bacterial wound infections is not well studied. In this Bacteriology of Infections in Taiwanese snake Envenomation (BITE) study, we investigated the prevalence of wound infection, bacteriology, and corresponding antibiotic usage in patients presenting with snakebites from these two snakes. We further developed a BITE score to evaluate the probability of wound infections and guide antibiotic usage in this patient population. All snakebite victims who presented to the emergency departments of seven training and research hospitals and received at least one vial of freeze-dried hemorrhagic antivenin between January 2001 and January 2017 were identified. Patient biodata, laboratory investigation results, and treatment modalities were retrieved. We developed our BITE score via univariate and multiple logistic regression analyses. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive performance of the BITE score. Out of 8,295,497 emergency department visits, 726 patients presented with snakebites from a Taiwan habu or a green bamboo viper. The wound infection rate was 22.45%, with seven positive wound cultures, including six polymicrobial infections. Morganella morganii, Enterococcus spp., Bacteroides fragilis, and Aeromonas hydrophila were most frequently cultured. There were no positive blood cultures. A total of 33.0% (n = 106) of snakebite patients who received prophylactic antibiotics nevertheless developed wound infections, while 44.8% (n = 73) of wound infection patients were satisfactorily treated with one of the following antibiotics: amoxicillin/clavulanic acid, oxacillin, cefazolin, and ampicillin/sulbactam. With the addition of gentamicin, the success of antibiotic therapy increased by up to 66.54%. The prognostic factors for the secondary bacterial infection of snakebites were white blood cell counts, the neutrophil lymphocyte ratio, and the need for hospital admission. The area under the ROC curve for the BITE score was 0.839. At the optimal cut-off point of 5, the BITE score had a 79.58% accuracy, 82.31% sensitivity, and 79.71% specificity when predicting infection in snakebite patients. Our BITE score may help with antibiotic stewardship by guiding appropriate antibiotic use in patients presenting with snakebites. It may also be employed in further studies into antibiotic prophylaxis in snakebite patients for the prevention of superimposed bacterial wound infections.

Four types of antivenom are used to treat snakebites by the six species of venomous snakes native to Taiwan. Research into antivenom use in Taiwan and its outcomes, as well as the utility of current Taiwan Poison Control Center guidelines for antivenom use, has been limited. We aimed to provide increased understanding by investigating the treatment and outcomes of patients treated for snakebite in Taiwan. On the basis of data collected from the 2009 Taiwan National Health Insurance database, patients with snakebites were identified and categorized into two sets of groups according to types of antivenom administered. The relationships between antivenom types, dosage and the variables of antibiotic use, surgical intervention, acute respiratory failure acute, renal failure, antivenom-related allergic reaction, mortality, need for hospital admission, and length of hospitalization were analyzed by multivariate logistic regression and the Kruskal-Wallis test. The majority of patients were successfully treated by administration of 1 vial of antivenom and discharged without complications. However, patients treated for neurotoxic-type venom snakebite required administration of larger doses of antivenom and > 30% required surgical intervention, particularly those treated for Chinese cobra snakebite. Approximately 10% of patients were administered two types of antivenom. The results partially support Taiwan Poison Control Center guidelines for treating the hemorrhagic-type venom snakebite. However, deficit in the guidelines for treatment of neurotoxic-type venom snakebite is obvious and new guidelines for treatment of neurotoxic-type venom snakebite and diagnosis should be developed.