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Fulltext Cross neutralization of Afro-Asian cobra and Asian krait venoms by a Thai polyvalent snake antivenom (Neuro Polyvalent Snake Antivenom)

Leong PK, Sim SM, Fung SY, Sumana K, Sitprija V, Tan NH

PLoS Negl Trop Dis, 2012;6(6):e1672.
PMID: 22679522 DOI: 10.1371/journal.pntd.0001672

BACKGROUND: Snake envenomation is a serious public health threat in the rural areas of Asian and African countries. To date, the only proven treatment for snake envenomation is antivenom therapy. Cross-neutralization of heterologous venoms by antivenom raised against venoms of closely related species has been reported. The present study examined the cross neutralizing potential of a newly developed polyvalent antivenom, termed Neuro Polyvalent Snake Antivenom (NPAV). NPAV was produced by immunization against 4 Thai elapid venoms.
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.

Matched MeSH terms: Antivenins/administration & dosage*
Fulltext Antivenom cross-neutralization of the venoms of Hydrophis schistosus and Hydrophis curtus, two common sea snakes in Malaysian waters

Tan CH, Tan NH, Tan KY, Kwong KO

Toxins (Basel), 2015 Feb;7(2):572-81.
PMID: 25690691 DOI: 10.3390/toxins7020572

Sea snake envenomation is a serious occupational hazard in tropical waters. In Malaysia, the beaked sea snake (Hydrophis schistosus, formerly known as Enhydrina schistosa) and the spine-bellied sea snake (Hydrophis curtus, formerly known as Lapemis curtus or Lapemis hardwickii) are two commonly encountered species. Australian CSL sea snake antivenom is the definitive treatment for sea snake envenomation; it is unfortunately extremely costly locally and is not widely available or adequately stocked in local hospitals. This study investigated the cross-neutralizing potential of three regionally produced anti-cobra antivenoms against the venoms of Malaysian H. schistosus and H. curtus. All three antivenoms conferred paraspecific protection from sea snake venom lethality in mice, with potency increasing in the following order: Taiwan bivalent antivenom < Thai monocled cobra monovalent antivenom < Thai neuro polyvalent antivenom (NPAV). NPAV demonstrated cross-neutralizing potencies of 0.4 mg/vial for H. schistosus venom and 0.8 mg/vial for H. curtus, which translates to a dose of less than 20 vials of NPAV to neutralize an average amount of sea snake venom per bite (inferred from venom milking). The cross-neutralization activity was supported by ELISA cross-reactivity between NPAV and the venoms of H. schistosus (58.4%) and H. curtus (70.4%). These findings revealed the potential of NPAV as a second-line treatment for sea snake envenomation in the region. Further profiling of the cross-neutralization activity should address the antivenomic basis using purified toxin-based assays.

Matched MeSH terms: Antivenins/administration & dosage
Epidemiology of sea-snake bites

Reid HA

J Trop Med Hyg, 1975 May;78(5):106-13.
PMID: 1152101

Epidemiological features as reflected by 101 patients with unequivocal sea-snake bite received in north-west Malaya are reviewed. Enhydrina schistosa caused over half the bites, including seven of the eight fatal bites. It is the most dangerous sea-snake to man. Over 90 per cent of the victims were male and 80 of the 101 patients were fishermen bitten at their job. Most victims were bitten on the lower limb through treading on the snake, and this resulted in more cases of serious poisoning than upper limb bites (caused through handling nets, sorting fish and so on). Only 14 cathers were bitten (through treading on the sea-snake; no bathers were bitten while swimming). In patients coming to hospital more than six hours after the bite, there was a four-fold increase in serious poisoning compared with patients coming within six hours of the bite. Thus, as time elapses after the bite, the victim is less likely to seek medical help unless poisoning is severe. Despite the lethal toxicity of sea-snake venom, in patients seen during 1957-61 before sea-snake antivenom became available, the mortality was only 10 per cent. Trivial or no poisoning followed in 80 per cent of the bites. On the other hand, of 11 patients (20 per cent) with serious poisoning, over half (six patients) died despite supportive hospital treatment. These epidemiological features observed in Malaya probably apply to most fishing folk along Asian coastlines where sea-snakes abound. If this is so, sea-snake bite must be a common hazard feared by millions of fishing folk, and a common cause of illness and death. But it is unlikely that the extent of this problem will be revealed to orthodox medicine for many decades because most fishing villages are far from medical centres; and even if hospitals or medical centres are available, fishing folk are usually reluctant to attend them. Only one species of sea-snake, Pelamis platurus, extends to the east coasts of Africa and west coasts of the tropical Americas, but for various reasons this species does not appear to constitute much of a hazard to fishing folk in these areas. Although bathers are occasionally bitten along Asian coasts, when they inadvertently tread on a sea-snake, the risk of sea-snake bite in this area is extremely low. The prevention of sea-snake bite and poisoning is considered. Highly effective antivenom is now available for treating victims with serious poisoning; death should not occur provided adequate medical treatment is given within a few hours of the bite. The main problem is provision of adequate medical care at rural medical centres and overcoming the reluctance fishing folk often have in attending these centres.

Matched MeSH terms: Antivenins/administration & dosage
The Effect of a Polyvalent Antivenom on the Serum Venom Antigen Levels of Naja sputatrix (Javan Spitting Cobra) Venom in Experimentally Envenomed Rabbits

Yap MK, Tan NH, Sim SM, Fung SY, Tan CH

Basic Clin Pharmacol Toxicol, 2015 Oct;117(4):274-9.
PMID: 25819552 DOI: 10.1111/bcpt.12398

The treatment protocol of antivenom in snake envenomation remains largely empirical, partly due to the insufficient knowledge of the pharmacokinetics of snake venoms and the effects of antivenoms on the blood venom levels in victims. In this study, we investigated the effect of a polyvalent antivenom on the serum venom antigen levels of Naja sputatrix (Javan spitting cobra) venom in experimentally envenomed rabbits. Intravenous infusion of 4 ml of Neuro Polyvalent Snake Antivenom [NPAV, F(ab')2 ] at 1 hr after envenomation caused a sharp decline of the serum venom antigen levels, followed by transient resurgence an hour later. The venom antigen resurgence was unlikely to be due to the mismatch of pharmacokinetics between the F(ab')2 and venom antigens, as the terminal half-life and volume of distribution of the F(ab')2 in serum were comparable to that of venom antigens (p > 0.05). Infusion of an additional 2 ml of NPAV was able to prevent resurgence of the serum venom antigen level, resulting in a substantial decrease (67.1%) of the total amount of circulating venom antigens over time course of envenomation. Our results showed that the neutralization potency of NPAV determined by neutralization assay in mice may not be an adequate indicator of its capability to modulate venom kinetics in relation to its in vivo efficacy to neutralize venom toxicity. The findings also support the recommendation of giving high initial dose of NPAV in cobra envenomation, with repeated doses as clinically indicated in the presence of rebound antigenemia and symptom recurrence.

Matched MeSH terms: Antivenins/administration & dosage*
Antivenom in sea-snake bit poisoning

Reid HA

Lancet, 1975 Mar 15;1(7907):622-3.
PMID: 47960

Among a series of 101 patients bitten by sea-snakes in Malaya in the years 1957-64, 80% were fishermen. Bathers and divers are occasionally bitten. Before sea-snake antivenom became available the mortality-rate (despite the high toxicity of sea-snake venom) was only 10%; however, of 11 with serious poisoning, 6 died. Subsequently 10 patients with serious poisoning received specific sea-snake antivenom; 2 patients, admitted moribund, temporarily improved but died, and 8 patients recovered dramatically. In serious poisoning the suitable dosage of intravenous sea-snake antivenom is 3000-10,000 units; in mild poisoning 1000-2000 units should suffice.

Matched MeSH terms: Antivenins/administration & dosage
The prevalence of hypersensitivity reactions to snake antivenoms administered in sultanah nur zahirah hospital from 2013 to 2016

Nur AS, Hamid F, Mohd Shahezwan AW, Mohd Zaki FS, Ahmad KI

Med J Malaysia, 2020 05;75(3):216-220.
PMID: 32467535

INTRODUCTION: Snakebite is an important medical emergency. Antivenoms remain the only proven treatment for snake envenoming. However, the use of antivenom is associated with hypersensitivity reactions. The aims of this study were to determine the prevalence and types of hypersensitivity reactions and types and outcomes of pharmacological and non-pharmacological treatments for antivenom reactions among snakebite patients that received antivenoms.
METHODS: This was a 4-year cross-sectional study of snakebite patients from January 2013 to December 2016 in Hospital Sultanah Nur Zahirah (HSNZ), Terengganu. Data was extracted from the Pharmacy Record on the usage of antivenom and patients of snakebites treated with antivenom were identified. Data of patients were then obtained from the electronic medical records.' Demographic details, clinical features and characteristics of antivenom reactions of patients were recorded in standardized data collection forms and analyzed using chi-square or Mann- Whitney U tests.
RESULTS: Of the 44 patients who received antivenom, 24 (54.5%) developed hypersensitivity reaction. All patients developed reaction early. No patient developed delayed (serum-sickness) reaction. Of the 24 patients, 14 (58.3%) had moderate to severe hypersensitivity reaction and 9 (37.5%) patients had mild reactions. Only one (4.2%) patient presented with bradycardia.
CONCLUSION: The prevalence of early hypersensitivity reaction to snake antivenom in HSNZ was relatively high. Healthcare providers should be aware of the appropriate method of preparing and administering antivenom, and the management for acute hypersensitivity reactions. This will optimize the management of snakebite and ensure patient safety.

Matched MeSH terms: Antivenins/administration & dosage
Cross neutralisation of Southeast Asian cobra and krait venoms by Indian polyvalent antivenoms

Leong PK, Tan NH, Fung SY, Sim SM

Trans R Soc Trop Med Hyg, 2012 Dec;106(12):731-7.
PMID: 23062608 DOI: 10.1016/j.trstmh.2012.07.009

Cross neutralisation of venoms by antivenom raised against closely-related species has been well documented. The spectrum of paraspecific protection of antivenom raised against Asiatic Naja and Bungarus (krait) venoms, however, has not been fully investigated. In this study, we examined the cross neutralisation of venoms from common Southeast Asian cobras and kraits by two widely used polyvalent antivenoms produced in India: Vins Polyvalent Antivenom (VPAV) and Bharat Polyvalent Antivenom (BPAV), using both in vitro and in vivo mouse protection assays. BPAV was only moderately effective against venoms of N. kaouthia (Thailand) and N. sumatrana, and either very weakly effective or totally ineffective against the other cobra and krait venoms. VPAV, on the other hand, neutralised effectively all the Southeast Asian Naja venoms tested, as well as N. naja, B. candidus and Ophiophagus hannah venoms, but the potency ranges from effective to weakly effective. In an in vivo rodent model, VPAV also neutralised the lethality of venoms from Asiatic Naja and B. candidus. In anesthetised rat studies, both antivenoms effectively protected against the N. kaouthia venom-induced cardio-respiratory depressant and neuromuscular blocking effects. Overall, our results suggest that VPAV could be used as alternative antivenom for the treatment of elapid envenomation in Southeast Asian regions including Malaysia, Thailand and certain regions of Indonesia.

Matched MeSH terms: Antivenins/administration & dosage