Snakebite Mitigation Project of the Madras Crocodile Bank/Centre for Herpetology, India: background and a brief summary of activities.

Snakebite is a serious problem in rural India where several highly venomous species are commonly found in and around agricultural areas where prey such as rodents and amphibians are abundant. Four snake species, referred to as the Big Four, are responsible for the most serious and fatal bites: spectacled cobra (Naja naja), Russell's viper (Daboia russelii), common krait (Bungarus caeruleus) and saw-scaled viper (Echis carinatus). A polyvalent antivenom is made to treat these bites but public awareness and distribution of this life-saving drug is inadequate. The Madras Crocodile Bank and its partners are conducting a snakebite project which includes venom sampling and research, snake and snakebite treatment centre mapping, and a nationwide awareness campaign for snakebite mitigation.

Neurological manifestations in speech after snake bite: a rare case.

The patient was admitted after reporting a snake bite from which he later developed neurological signs and symptoms among which a flaccid dysarthria. The patient underwent speech therapy and showed significant improvement over a short period of time. The favorable outcome of the present study highlights the role of speech therapy in such a case, where it often remains un-emphasized.

The greater black krait (Bungarus niger), a newly recognized cause of neuro-myotoxic snake bite envenoming in Bangladesh.

Prospective studies of snake bite patients in Chittagong, Bangladesh, included five cases of bites by greater black kraits (Bungarus niger), proven by examination of the snakes that had been responsible. This species was previously known only from India, Nepal, Bhutan and Burma. The index case presented with descending flaccid paralysis typical of neurotoxic envenoming by all Bungarus species, but later developed generalized rhabdomyolysis (peak serum creatine kinase concentration 29,960 units/l) with myoglobinuria and acute renal failure from which he succumbed. Among the other four patients, one died of respiratory paralysis in a peripheral hospital and three recovered after developing paralysis, requiring mechanical ventilation in one patient. One patient suffered severe generalized myalgia and odynophagia associated with a modest increase in serum creatine kinase concentration. These are the first cases of Bungarus niger envenoming to be reported from any country. Generalized rhabdomyolysis has not been previously recognized as a feature of envenoming by any terrestrial Asian elapid snake, but a review of the literature suggests that venoms of some populations of Bungarus candidus and Bungarus multicinctus in Thailand and Vietnam may also have this effect in human victims. To investigate this unexpected property of Bungarus niger venom, venom from the snake responsible for one of the human cases of neuro-myotoxic envenoming was injected into one hind limb of rats and saline into the other under buprenorphine analgesia. All animals developed paralysis of the venom-injected limb within two hours. Twenty-four hours later, the soleus muscles were compared histopathologically and cytochemically. Results indicated a predominantly pre-synaptic action (ß-bungarotoxins) of Bungarus niger venom at neuromuscular junctions, causing loss of synaptophysin and the degeneration of the terminal components of the motor innervation of rat skeletal muscle. There was oedema and necrosis of extrafusal muscle fibres in envenomed rat soleus muscles confirming the myotoxic effect of Bungarus niger venom, attributable to phospholipases A2. This study has demonstrated that Bungarus niger is widely distributed in Bangladesh and confirms the risk of fatal neuro-myotoxic envenoming, especially as no specific antivenom is currently manufactured. The unexpected finding of rhabdomyolysis should prompt further investigation of the venom components responsible. The practical implications of having to treat patients with rhabdomyolysis and consequent acute renal failure, in addition to the more familiar respiratory failure associated with krait bite envenoming, should not be underestimated in a country that is poorly equipped to deal with such emergencies.

Role of neostigmine and polyvalent antivenom in Indian common krait (Bungarus caeruleus) bite.

Bungarus caeruleus (Indian common krait) bite during monsoons is common in Northwest India. This study was undertaken to find the effectiveness of neostigmine and polyvalent antivenom in improving neuromuscular paralysis following bite. All the consecutive patients admitted between June 2007 and December 2008 with common krait bite, identified either from brought snake or circumstantial evidence were studied. Ten vials of polyvalent antivenom and three doses of 2.5 mg neostigmine at 30 min intervals after administration of 0.6 mg of atropine were administered I.V. and patients were assessed for any improvement in neuroparalysis. Seventy-two patients were admitted during the study period. All the patients except two came from rural areas and were brought between June and September. Sixty-two patients were bitten during the day while clearing bricks, cutting grass or walking. The mean time interval between bite and arrival to hospital was 4.5 h. None of the patients showed any improvement following treatment and all patients developed respiratory paralysis, requiring assisted ventilation. Seventy survived and two died. Neostigmine is ineffective in reversing or improving neuroparalytic features in patients with B. caeruleus bite even at higher dose than normally recommended.

Hyponatraemia, rhabdomyolysis, alterations in blood pressure and persistent mydriasis in patients envenomed by Malayan kraits (Bungarus candidus) in southern Viet Nam.

Between 1998 and 2007, 42 patients admitted to Choray hospital, Ho Chi Minh City, and to two hospitals in adjacent regions in southern Viet Nam brought the Malayan kraits (Bungarus candidus) that had been responsible for biting them. Half of the patients had been bitten while they were asleep. Fang marks and numbness were the only local features of the bites. Common signs of neurotoxic envenoming included bilateral ptosis, persistently dilated pupils, limb weakness, breathlessness, hypersalivation, dysphonia and dysphagia. Thirty patients (71.4%) required endotracheal intubation of whom all but one were mechanically ventilated. Fourteen patients (33.3%) developed hypertension, 13 (31.0%) shock, 31 (73.8%) hyponatraemia (plasma sodium concentration < 130 mEq/l) and 30 (71.4%) showed evidence of mild rhabdomyolysis (peak plasma creatine kinase concentration 1375 +/- 140 micro/l). None developed acute kidney injury. All the patients were treated with a new monospecific B. candidus antivenom. There were no fatalities. Hyponatraemia has been reported previously in victims of Chinese kraits (Bungarus multicinctus) in northern Viet Nam and rhabdomyolysis in patients envenomed by B. niger in Bangladesh. These features of envenoming pose new problems for the management of krait bite cases in South east Asia and should stimulate a search for the causative venom toxins.

Specific antivenom for Bungarus candidus.

BACKGROUND: Bungarus candidus (Malayan krait) snake is a neurotoxin snake. Previous treatment after snakebite was mainly respiratory support until the patient had spontaneous breathing. Recently specific antivenom for the Bungarus candidus snake was produced by the Queen Saovabha Memorial Institute and distributed in June 2004. The present article is the first report on the clinical response to the specific antivenom for Bungarus candidus. OBJECTIVE: To analyze the signs and symptoms of patients after snakebite and the response of the patients after receiving specific antivenom for Bungarus candidus snake. STUDY DESIGN: Retrospective chart review. MATERIAL AND METHOD: Four cases of Bungarus candidus snakebite were identified and divided into two groups. Group I (Case 1, 2, and 3) had received specific antivenom for Bungarus candidus while group 2 (case 4) had not. Onset, signs and symptoms after snakebite, antivenom dosage, and response time after receiving antivenom were analyzed. RESULTS: The first three patients received specific antivenom for Bungarus candidus and the fourth patient did not receive any. All four patients developed neurological signs and symptoms from this neurotoxic venom. In case 1, 2, and 4, the first signs and symptoms were dyspnea, difficulty with speech, and opening the eyelids at 50 minutes (30-60 minutes). The onset ofother signs and symptoms included respiratory paralysis with intubation 3 hours (2-4 hours), full ptosis 3.66 hours (3-4 hours), mydriasis and fixedpupils 4.33 hours (4-5 hours), no response to stimuli 5.66 hours (4-10 hours), tachycardia 5.5 hours (47 hours), and hypertension 14 hours (4-24 hours). The first two patients received specific antivenom for Bungarus candidus after being bitten at 10 and 12 hours, respectively. The first clinical response in case 1, were 12 hours after receiving 16 vials, and in case 2, were 20 hours after receiving 16 vials. These were slight movement of feet phalanxes. At 40 hours after receiving specific antivenom 30 vials in case 1 and 32 vials in case 2, they were able to respond to commands, motor power changed from grade 0 to grade 1 and there was 50% elevated eyebrows. The motor power changedfrom grade I to grade 4 with 100% elevation of eyebrows from full ptosis was 65 hours after receiving specific antivenom 60 vials in case 1 and 70 hours after receiving specific antivenom 87 vials in case 2. The patients had spontaneous opening ofeyelids at 90 hours after receiving 80 vials for case I and 88 hours after receiving 87 vials for case 2. Case 2 was extubated on day 4 after the snakebite while case 1 was extubated later on day 10 because of superimposing pneumonia. The third case had delayed onset of signs and symptoms of neurotoxicity compared to the other three patients. Dyspnea, difficulty with speech, and opening eyelids occurred at 5 hours after the snakebite. No response to stimuli and respiratory paralysis occurred at 20 hours after the snakebite. His consciousness improved 10 hours after receiving 3 vials of specific antivenom. This was noted by being able to respond to commands and the motor power changed to grade 2 however, full ptosis was still present up to 24 hours. After receiving 23 vials ofspecific antivenom, he accidentally extubated himself however, he could breathe adequately using a mask with a bag. His motor power changed to grade 4 with 100% elevated eyebrows but full ptosis 34 hours after receiving 38 vials of specific antivenom. He could spontaneously open his eyelids 40 hours after receiving 38 vials specific antivenom. Cases 1, 2, and 3 had persistent mydriasis andfixed pupils until discharge. Case 4 did not receive specific antivenom for Bungarus candidus. He did not respond to stimuli 10 hours after snakebite and he was treated with respirator and symptomatic treatment. On day 2, his blood pressure dropped, he was on dopamine to raise his BP On day 3, he developed ventricular fibrillation. Defibrillation was administered and ECG returned to normal. He was given further supportive care. On day 7, he was discharged at the request of his relatives without any improvement. CONCLUSION: The patients who received specific antivenom had more rapid improvement ofsigns and symptoms comparing to the patient who did not receive the antivenon.

Envenoming bites by kraits: the biological basis of treatment-resistant neuromuscular paralysis.

Beta-bungarotoxin, a neurotoxic phospholipase A2 is a major fraction of the venom of kraits. The toxin was inoculated into one hind limb of young adult rats. The inoculated hind limb was paralysed within 3 h, and remained paralysed for 2 days. The paralysis was associated with the loss of synaptic vesicles from motor nerve terminal boutons, a decline in immunoreactivity of synaptophysin, SNAP-25 and syntaxin, a loss of muscle mass and the upregulation of NaV(1.5) mRNA and protein. Between 3 and 6 h after the inoculation of toxin, some nerve terminal boutons exhibited clear signs of degeneration. Others appeared to be in the process of withdrawing from the synaptic cleft and some boutons were fully enwrapped in terminal Schwann cell processes. By 12 h all muscle fibres were denervated. Re-innervation began at 3 days with the appearance of regenerating nerve terminals, a return of neuromuscular function in some muscles and a progressive increase in the immunoreactivity of synaptophysin, SNAP-25 and syntaxin. Full recovery occurred at 7 days. The data were compared with recently published clinical data on envenoming bites by kraits and by extrapolation we suggest that the acute, reversible denervation caused by beta-bungarotoxin is a credible explanation for the clinically important, profound treatment-resistant neuromuscular paralysis seen in human subjects bitten by these animals.

Envenoming by Chinese krait (Bungarus multicinctus) and banded krait (B. fasciatus) in Myanmar.

A retrospective study of 8 cases of envenoming by Chinese krait (Bungarus multicinctus) and one banded krait (B. fasciatus) in southern Myanmar is reported. Chinese krait bite produced minimal local reactions, except in one person bitten on the lip which resulted in local swelling. Onset of neurotoxic symptoms occurred 2.5-6 h after the bite, and the interval between bite and death ranged from 12-30 h. Three deaths were due to respiratory failure. Four mildly envenomed cases recovered spontaneously without assisted ventilation. One severely envenomed patient recovered after 8 d intensive respiratory care. Cobra (Naja kaouthia) antivenom had no value in reversing neurotoxic symptoms. Anticholinesterase injection given to one patient failed to improve neurotoxic symptoms. The bite of banded krait (B. fasciatus) resulted in neurotoxic envenoming within 2 h after the bite, with minimal local reactions. The victim died of respiratory failure 14 h after the bite.