Studies

Bungarus candidus
Eastern Thailand/Northwestern Malaysia
Warrell et al. 1983: 5 patients bitten by B. candidus. Identification: morphological 4/5, B. candidus venom antigen with ELISA 1/5.

No envenoming 2/5.

Systemic (neurotoxic) envenoming 3/5, 1 of whom died.

All data below relate to the 3 patients with systemic envenoming.  

 

Southern Vietnam

Trinh et al 2010: 42 patients bitten by B. candidus. Identifiation: morphological 42/42.

Systemic envenoming 42/42.

 

Bungarus caeruleus
Sri Lanka

Theakston et al. 1990b: 5 patients bitten by B. caeruleus. Identification: morphological 2/5, B. caeruleus venom antigen with ELISA (3/5).

No envenoming 1/5, systemic (neurotoxic) envenoming 4/5. All data below relate to the 4 patients with systemic envenoming.

Ariaratnam et al 2008: 88 patients bitten by B. caeruleus. Identification: morphological 88/88.

 

Bungarus niger
Bangladesh

Faiz et al 2010: 5 patients bitten by B. niger. Identification: morphological 5/5.

 

Studies in which the species was not clearly identified or evidence for the identification was lacking

Bungarus fasciatus
China
Sawai et al. 1992: 26 B. fasciatus bites are described without details of the identification criteria.

 

Bungarus multicinctus
China

Sawai et al. 1992: 80 B. multicinctus bites are described without details of the identification criteria.

Myanmar

Pe et al 1997: 8 patients bitten by B.multicinctus. Identification: "positively" identified 2/8.

Vietnam

 

Hung et al 2009: 60 patient bitten by B. multicinctus. Identification: morphological; by patient; circumstances and clinical features; B. multicinctus only krait of medical relevance in the region.

 

Bungarus caeruleus

Indien

Bawaskar und Bawaskar 2004: 23 patients bitten by kraits. Identification: indirect evidenc (bite at night whilst sleeping on the floor, abdominal pain, no local signs, neurotoxic signs and symptoms). 4/23 reported with snake available for identification.

 

Bungarus spp.
India
Sethi and Rastogi 1982: 5 cases are described. In 3 the snakes are said to have been definitely recognised as 'banded kraits', in the other 2 'banded kraits' were assumed to be the cause.

Case reports

Bungarus caeruleus
Sri Lanka
Fernando and Dias 1982: 1 case; morphological identification.
Haast and Winer 1955: 1 case; morphological identification.

India
Ahuja and Singh 1954: 2 cases; morphological identification.

Bungarus ceylonicus
Sri Lanka
de Silva et al. 1993: 1 case; morphological identification; review of the literature.
Karalliedde and Sanmuganathan 1988: 1 case; no identification criteria specified.

Bungarus fasciatus
Thailand
Viravan et al. 1986: 1 patient; identification: detection of venom antigen in serum by ELISA.

Bungarus multicinctus
Taiwan
Kuo and Wu 1972: 6 patients whose bites were attributed to B. multicinctus. In this paper there are no details of the basis on which the species was identified; the paper includes 2 detailed case reports.

 

Vietnam

Höjer et al 2010: 1 patient bitten by B. multicinctus. Identiication: Signs and symptoms typical for a B. multicinctus bite.

 

Signs & symptoms

Local effects

Bungarus candidus
Mild pain at the site of the bite 1/3 (Warrell et al. 1983).
Swelling at the site of the bite 0/3 (Warrell et al. 1983).

Fangmarks visible 42/42. Local numbness 15/42 (Trinh et al 2010).

Bungarus caeruleus
Mild pain or itching at the site of the bite 3/4 (Theakston et al. 1990b).
Swelling at the site of the bite 0/4, bite marks barely visible or not at all (Theakston et al. 1990b).
Painful regional lymph nodes 2/4 (Theakston et al. 1990b).

8/88 mild local swelling (Ariaratnam et al 2008).

 

Bungarus fasciatus
Local pain and swelling (Viravan et al. 1986).

Bungarus multicinctus
Local pain and swelling 0/6. However, 1 patient noticed a needle-like prick at the time of the bite (Kuo and Wu 1972).
Swelling of the regional lymph nodes 0/6 (Kuo and Wu 1972).

Local pain and swelling 1/8 (Pe et al 1997).

Neurological effects

Bungarus candidus
Preparalytic phase 75 min–3 h (3/3), but can last up to 12 h (Warrell et al. 1983).
Ptosis 3/3, ophthalmoplegia 2/3, ophthalmoplegia not confirmed or not tested 1/3, paralysis of the masticatory musculature, glossopharyngeal and respiratory paralysis 2/3, tetraparesis 2/3, tetraparesis not confirmed or not tested 1/3 (Warrell et al. 1983).
Parasympathetic findings 1/3, not confirmed or not tested 2/3: dilated, fixed pupils (reduced constrictive effect of pilocarpine), heart rate consistently >120/min during the paralytic phase, no reduction in blood pressure or heart rate with a change in position or carotid sinus massage (indicates the cholinergic blocking effect of krait venom) (Warrell et al. 1983).

Dilated pupils 42/42, ptosis 42/42, limb weakness 42/42, breathlessness 42/42, hypersalivation 39/42, dysphonis 38/42, dyphagia 36/42, numbness of lips 23/42 (Trinh et al 2010).

 

Bungarus caeruleus
Preparalytic phase 1–7 h 4/4 (Theakston et al. 1990b).
Ptosis 1.5 h after the bite 4/4 (Theakston et al. 1990b).
Bilateral external ophthalmoplegia 1.5 h after the bite 3/4 (Theakston et al. 1990b).
Respiratory failure (paralysis of the respiratory musculature) 1/4 (Theakston et al. 1990b).
Progressive signs of paralysis with respiratory failure 2/2 (Ahuja and Singh 1954).

Respiratory paralysis 56/88, abdominal pain 80/88 (Ariaratnam et al 2008).

Bungarus ceylonicus
Paralysis of the respiratory musculature and respiratory failure 6 h after the bite.  Dysphagia preceded these symptoms by a number of hours (Karalliedde and Sanmuganathan 1988).
Progressive paralysis with respiratory failure commenced within an hour after the bite (de Silva et al. 1993).

Bungarus fasciatus
Ptosis, paralysis of the respiratory musculature with respiratory failure (Viravan et al. 1986).
Signs of paralysis 6/26 (Sawai et al. 1992).

Bungarus multicinctus
Ptosis 4/6 (Kuo and Wu 1972).
Paralysis of the respiratory musculature (dyspnoea and respiratory failure) in 4/6 patients, 3 of whom died (Kuo and Wu 1972).
Signs of paralysis (29/80) (Sawai et al. 1992).

Neurotoxic signs and symptoms (Pe et al 1997).

Typical neurotoxic signs and symptoms. Ptosis 56/60, respiratory muscles (dyspnoea) 52/60 (Hung et al 2009).

 

Bungarus niger

Neurotoxic signs and symptoms 5/5 (Faiz et al 2010).

Muscular effects

Bungarus caeruleus
Intense, prolonged muscular pain that reached a maximum on the 2nd day in hospital, with tenderness in the musculature of the extremities and trunk as well as the masseter (2/4). The plasma myoglobin concentration was raised in one of the two patients. Presynaptically active (β)phospholipase A₂ bungarotoxin as the cause of generalized rhabdomyolysis? (Theakston et al. 1990b). Muscular pain and spasms (Haast and Winer 1955).

 

Bungarus candidus
Tenderness of the musculature and muscle pain with passive movement; however, generalized rhabdomyolysis was excluded by means of laboratory tests (Warrell et al. 1983).

Myalgia was not recorded in the case notes (Trinh et al 2010).

 

Bungarus niger

Severe generalized myalgia and odynophagia 1/5 (Faiz et al 2010).

 

Bungarus multicinctus

Generalized myalgia 41/60 (Hung et al 2009).

Other signs & symptoms

Bungarus candidus

Shock 13/42 (hypotension may be linked to hyponatraemia and the possibility of venom natriuretic peptide activity) (Trinh et al 2010).

Bungarus caeruleus
Stomach pain 1/4 (Theakston et al. 1990b).
Stomach cramps (Fernando and Dias 1982).
Stomach cramps, nausea, vomiting (4 h after the bite)  (Haast and Winer 1955).

Bungarus multicinctus
Nausea, vomiting or stomach pain 3/6 (Kuo and Wu 1972). Aetiology unclear. In one patient, nausea and vomiting developed 30 min after the bite.

Case fatality rate

Bungarus candidus
1/3 as a result of cerebral anoxia (Warrell et al. 1983).
According to a study on fatal snakebites in rural areas of Thailand, 13/46 victims died from B. candidus bites. The cause of death in all 13 victims was respiratory failure. The surprising part of these findings was that of the 46 fatal snakebites studied, the incidence of fatal B. candidus bites was just as high as those from C. rhodostoma and N. kaouthia (Looareesuwan et al. 1988).

0/42 (Trinh et al 2010).

Bungarus caeruleus
0/4 (Theakston et al. 1990b). 27 fatalities in Sri Lanka in patients who were bitten by B. caeruleus and treated by traditional methods (de Silva 1987b). Mortality rate of 77% in 35 patients in India confirmed to have been bitten by B. caeruleus and not treated with antivenom (Ahuja and Singh 1954).

5/88 (Ariaratnam et al 2008).

Bungarus ceylonicus
1 fatality (de Silva et al. 1993).

Bungarus fasciatus
According to a study on fatal snakebites in rural areas of Thailand, 1/46 victims died from a B. fasciatus bite. The cause of death was respiratory failure. The patient was mistakenly given cobra antivenom (Looareesuwan et al. 1988).
6/26 patients with signs of paralysis, 2 of whom died (Sawai et al. 1992).

 

Bungarus multicinctus
3/6 (Kuo and Wu 1972). In Taiwan (1904–1971): 213/925 (Kuo and Wu 1972).
29/80 with signs of paralysis, 8 of whom died (Sawai et al. 1992).

3/8 (Pe et al 1997).

1/1 due to severe hyponatremia-induced brain damage (Höjer et al 2010).

 

Bungarus niger

2/5 (Faiz et al 2010).

Morbidity

As long as no problems arise in connection with the neuromuscular paralysis, in particular the paralysis of the respiratory musculature (hypoxic brain injury), no long-term sequelae are to be expected.

Laboratory and physical investigations

1.  Leucocytes

Bungarus candidus: leucocytosis 3/3 (minimum 13,300/mm³, maximum 22,400/mm³ (Warrell et al. 1983).
Bungarus caeruleus: mild leucocytosis 2/4 (Theakston et al. 1990b).
Bungarus multicinctus: leucocytosis 2/3 (Kuo and Wu 1972).

 

2. Serum creatine kinase

Bungarus candidus: above normal 30/42, peak levels 1375 ± 140 u/l (Trinh et al 2010).

Bungarus niger: peak serum creatine kinase 29 960 u/l with myoglobulinuria (rhabdomyolysis) and acute renal failure 1/5; modest increase of serum creatine kinase 1/5  (Faiz et al 2010).

 

3. Hyponatremia

Bungarus multicinctus: severe hyponatremia (dropping to 104 mmol/l within 48h) 1/1 (Höjer et al 2010)

Bungarus multicinctus: hyponatremia 25/60 (Hung et al 2009).

 

4. ELISA

One patient with neurotoxic signs of envenoming received QSMI cobra antivenom and died. Serum ELISA analysis revealed B. fasciatus venom antigen (Viravan et al. 1986) (see Biomedical database entry for N. kaouthia and Diagnosis & Treatment: Terrestrial snakes: Indian Subcontinent and Southeast Asia).

 

Treatment (symptomatic)

1. Artificial respiration (manual/machine):
Successful manual ventilation by relatives and nurses over a period of 49 h (Warrell et al. 1983).
Successful outcome after 78 h of ventilation (Karalliedde and Sanmuganathan 1988); after 18 h of ventilation (Fernando and Dias 1982).

Mechanical ventilation required for an average of 48h 29/42, all successful (Trinh et al 2010).

Recommendation: endotracheal intubation and/or artificial respiration (manual/machine) must be performed in patients with bulbar paralysis and paralysis of the respiratory musculature and is the only method with a demonstrated chance of success.

 

2. Acetylcholinesterase inhibitors 
Bungarus candidus
Achieved marked and lasting improvement in 1/3 patients, i.e. neither the parasympathetic cholinergic nerve endings nor the motor end plates were completely blocked. This treatment was ineffective in 1/3 patients and not administered in 1/3 (Warrell et al. 1983).

 

Bungarus caeruleus

Edrophonium was given to 2/4 patients, but with no improvement in the neurological symptoms. Differences in efficacy can be explained by the relationship between pre- and postsynaptic toxins in individual cases of envenoming or by neuromuscular blockade already being present at the time at which treatment is administered (Theakston et al. 1990b).

Bungarus ceylonicus
Edrophonium had no apparent effect (de Silva et al. 1993; Karalliedde and Sanmuganathan 1988).

Bungarus sp. (India)
Edrophonium had no apparent effect (Sethi and Rastogi 1982).

Recommendation: edrophonium (Tensilon®) test in all cases with neurotoxic signs and symptoms. If positive, proceed with acetylcholinesterase inhibition.

Treatment (specific)

Antivenom efficacy

Bungarus candidus
Paraspecific antivenoms: 1. Polyvalent antisnake venom serum (Haffkine, Mumbai): administered i.v. to 1/3 patients with a possible effect. 2. Banded krait antivenom (QSMI, Bangkok): administered i.v. to 1/3 patients with no effect (Warrell et al. 1983).

Bungarus caeruleus
Polyvalent antisnake venom serum (Haffkine, Mumbai): 3/4 patients received 10 vials i.v., 1/4 patients received 34 vials i.v. Antigenaemia was no longer evident within 1 h of administration of antivenom, although it re-appeared in 1/4 patients after one day. No satisfactory clinical success observed in any of the 4 patients (Theakston et al. 1990b). No apparent effect of antivenom (Fernando and Dias 1982).

Polyspecific antivenom (Haffkine) (84/88) according to national guidelines published by the Sri Lanka Medical Association 1983 without convincing effect (Ariaratnam et al 2008).

Bungarus ceylonicus
Polyvalent antisnake venom serum (Haffkine, Mumbai) had no apparent effect in the 2 cases in which it was administered (de Silva et al. 1993; Karalliedde and Sanmuganathan 1988).

Bungarus multicinctus
Taiwan
1. Bungarus antivenom (National Institute of Preventive Medicine, Taipei): in 1 patient 40 ml i.v. had no effect (Kuo and Wu 1972).
2. Naja-Bungarus antivenom (National Institute of Preventive Medicine, Taipei): in 1 patient 20 ml i.v. had no effect (Kuo and Wu 1972).
China
Antivenom given to 12 patients with signs of paralysis, 3 of whom died. The time interval between the bite and death was 67–168 h (Sawai et al. 1992).
No antivenom administered to 17 patients with signs of paralysis, 5 of whom died. The time interval between the bite and death was 6–23 h (Sawai et al. 1992).

 

Recommendations

Bungarus candidus
The paraspecific polyvalent antisnake venom serum (Haffkine, Mumbai) is of doubtful value.

Bungarus caeruleus
Given the present state of knowledge (i.e. until the anti-neurotoxic effect of the antivenom is improved and there have been further studies regarding its clinical efficacy), polyvalent antisnake venom serum (Haffkine, Mumbai) should be given at an initial dose of ≥100 ml (dose to be repeated every couple of hours, if no effect is seen, up to a maximum dose of 300 ml) in patients with neurotoxic signs and symptoms (Theakston et al. 1990b).

No convincing evidence for the efficacy of the anivenom given because of high binding affinity of the toxins to the neural receptors. Early treatment with large doses may be effective, but clinical trials are needed to confirm this (Ariaratnam et al 2008).