PRINCIPAL FINDINGS: In vitro neutralization study using mice showed that NPAV was able to neutralize effectively the lethality of venoms of most common Asiatic cobras (Naja spp.), Ophiophagus hannah and kraits (Bungarus spp.) from Southeast Asia, but only moderately to weakly effective against venoms of Naja from India subcontinent and Africa. Studies with several venoms showed that the in vivo neutralization potency of the NPAV was comparable to the in vitro neutralization potency. NPAV could also fully protect against N. sputatrix venom-induced cardio-respiratory depressant and neuromuscular blocking effects in anesthetized rats, demonstrating that the NPAV could neutralize most of the major lethal toxins in the Naja venom.
CONCLUSIONS/SIGNIFICANCE: The newly developed polyvalent antivenom NPAV may find potential application in the treatment of elapid bites in Southeast Asia, especially Malaysia, a neighboring nation of Thailand. Nevertheless, the applicability of NPAV in the treatment of cobra and krait envenomations in Southeast Asian victims needs to be confirmed by clinical trials. The cross-neutralization results may contribute to the design of broad-spectrum polyvalent antivenom.
METHODS: The selected subjects were patients of all ages with a chief complaint of snakebite who presented to participating emergency departments (EDs) between 1 January 2011 and 31 December 2016.
RESULTS: A total of 1335 patients were eligible for the study. There were an average of 223 snakebite cases reported each year. Most snakebites occurred during the summer months (55.9%) in patients aged 40-59 y (36.3%) and males (61.5%). Snakebites occurred most frequently on Mondays (22.9%) between 12:00 and 17:59 h (42.0%) outdoors (57.9%) and in farm areas (20.7%). Over 82% of the bites were by venomous snakes across all seasons, and 66% of the patients visited EDs without using emergency medical services. Based on the excess mortality ratio-adjusted injury severity score, 88, 9.2 and 2.8% had mild, moderate and severe injuries, respectively. There were 10 fatalities during the study period.
CONCLUSION: This study provides essential information to understand and assess the burden and distribution of snakebites in South Korea and provides valuable information for developing appropriate prevention and control interventions to address it.
METHODOLOGY/PRINCIPLE FINDINGS: The D. siamensis monovalent antivenom displayed extensive recognition and binding to proteins found in D. siamensis venom, irrespective of the geographical origin of those venoms. Similar immunological characteristics were observed with the Hemato Polyvalent antivenom, which also uses D. siamensis venom as an immunogen, but binding levels were dramatically reduced when using comparator monovalent antivenoms manufactured against different snake species. A similar pattern was observed when investigating neutralization of coagulopathy, with the procoagulant action of all four geographical venom variants neutralized by both the D. siamensis monovalent and the Hemato Polyvalent antivenoms, while the comparator monovalent antivenoms were ineffective. These in vitro findings translated into therapeutic efficacy in vivo, as the D. siamensis monovalent antivenom was found to effectively protect against the lethal effects of all four geographical venom variants preclinically. Assessments of in vivo nephrotoxicity revealed that D. siamensis venom (700 μg/kg) significantly increased plasma creatinine and blood urea nitrogen levels in anaesthetised rats. The intravenous administration of D. siamensis monovalent antivenom at three times higher than the recommended scaled therapeutic dose, prior to and 1 h after the injection of venom, resulted in reduced levels of markers of nephrotoxicity and prevented renal morphological changes, although lower doses had no therapeutic effect.
CONCLUSIONS/SIGNIFICANCE: This study highlights the potential broad geographical utility of the Thai D. siamensis monovalent antivenom for treating envenomings by the Eastern Russell's viper. However, only the early delivery of high antivenom doses appears to be capable of preventing venom-induced nephrotoxicity.