Friday 20 January 2017

(III) VSofI: Naja Kaouthia / Toxinology.com

The WHO includes in Category 1 two more snakes: Monocled Cobra (Naja Kaouthia) and Hump-nosed pit viper.
As it is quite extensive, this post will be dedicated exclusively to Naja Kaouthia and next to Hypnale Hypnale.



MONOCLED COBRA (Naja kaouthia)

MONOCLED COBRA, MONOCELLATED COBRA
(Naja Kaouthia), LESSON 1831.
Found in all North-east states, above Gangetic plains (Uttar Pradesh, Uttrakhand), Odisha, parts of Chota Nagpur (eastern Chattisgarh, whole of Bihar and Jharkhand), Haryana (probably the western most limit of this species). 
Outside India:

Bangladesh, Myanmar (= Burma), Cambodia, NE India (Uttar Pradesh, Bihar, Sikkim, Assam, West Bengal, Orissa), Bhutan, Laos, N Malaysia,
Nepal (?), S China, Thailand, S Vietnam

Venom type: Neurotoxic. 
Treatment: Polyvalent AV can be partially effective / symptomatic


Monocled Cobra (Naja Kaouthia) geographical distribution in India. IndianSnakes.org

http://reptile-database.reptarium.cz/species?genus=Naja&species=kaouthia&search_param=%28%28search%3D%27naja+kaouthia%27%29%29


Here is the synthesis of a good article on Monocled Cobra.
Please, always refer to the original article:
http://pubmedcentralcanada.ca/pmcc/articles/PMC3861878/


Biochemical and biological characterization of Naja Kaouthia venom from North-East India and its neutralization by polyvalent antivenom.


D. Das, N. Urs, V. Hirimath, B.S. Vishwanath, R. Doley.
J Venom Res. 2013; 4: 31–38.

ABSTRACT:
This study describes biochemical and biological properties of Naja Kaouthia (Indian monocled cobra) venom of North-East India. The DL50 of the crude venom was found to be 0.148mg/kg and neurotoxic symptoms like paralysis of lower limbs and heavy difficulty in breathing at sub-lethal dose in mice was observed. The venom exhibited PLA2, indirect hemolytic and myotoxic activities but showed weak proteolytic and low direct hemolytic activities. It did not exhibit any hemorrhage when injected intradermally to mice. Anticoagulant activity was prominent when recalcification, prothrombin and activated partial thrombinplastin time were tested on platelet poor plasma. Rotem analysis of whole citrated blood was depleted by venom when analyzed in Sonoclot. Crude venom at 10μg and after 16h of incubation was found to degrade α-chain of fibrinogen. Neutralization study showed that Indian polyvalent antivenom could neutralize some of the biochemical and biological activities as well as its fibrinogenolytic activity. 

In addition to the "Big Four", there might be other medically important snakes in specific geographical locations, which need attention. This is important for clinical diagnosis for treatment and for production of effective antivenoms. In India, polyvalent antivenom is raised against the "Big Four" venoms but these snakes may not be present throughout the country; Moreover, administration of this polyvalent antivenom has well documented limitations. 

Naja Kaouthis is recognized phenotypically with the presence of O-shaped or monocellate hood pattern. They are widely distributed in Nepal, North East India, Bangladesh, Myanmar, Thailand and Peninsular Malysia.


According to WHO, it belongs to Category 1 of venomous snakes. The symptoms of cobra bite are general neurotoxicity leading to flaccid paralysis and death by respiratory failure, and also severe hypertension. Symptoms of coagulopathy have also been reported.

The authors collected venom from adult Naja kaouthia form Jamugurihat, distric Sonitpur, Assam, North-East India and performed the following test:


  • Venom in vitro test: Total protein content, Phospholipase A2 (PLA2) activity, Caseinolytic activity,  direct and indirect hemolytic activity, Fibrinogenolytic activity, In-vitro coagulant assays: Recalcification time, Prothombin time (PT), Activated partial trhombin time (aPTT).
  • Whole citrated blood analysis.
    • Thromboelastometry analysis (Rotem)
    • Sonoclot analysis
  • Neutralization studies of the antivenom
  • Venom in vivo (mice) test: LD50, Edema inducing activity, Hemorrhagic activity, in-vivo myotoxicity (release of CK and LDH)

RESULTS:
LD50 (Median lethal dose) was found to be 0.148 mg/kg when injected intraperitoneally to experimental mice. When sub-lethal dose of venom was injected to mice, neurotoxic symptoms like difficulty in movement, breathing and frequent drinking of water were observed followed by death after 40 min. 
The amount of CK (in vivo-myotoxicity) released from muscles was 10 times more than for control mice. 
PLA2 activity was 7.6 μmol/min/mg (high activity)
The venom showed weak proteolitic activity (casein test). 
The venom showed anticoagulant activity in dose dependent manner. 

DISCUSSION:
Understanding the biochemical and biological properties of snake venom from a particular geographic location is important.


  • The LD50 of the Naja Kaouthia venom was found to be 0.149 mg/kg, whereas those for cobra venoms of Thailand and Kolkata origin were reported to be 0.23 mg/kg and 0.7 mg/kg respectively. The lethal dose of North East origin venom was less that that of the other geographical locations suggesting in might be more lethal.
  • In mice the venom did not induce haemorrhagic activity (which is more abundantly found in viper venom).
  • Edema inducing activity was not found to be significant. 
  • The high results for PLA2 suggest the presence of enzymatically active PLA2 in the venom. PLA2 is one of the major constituent in the elapid venom, which confers multiple toxicity to the prey or victim such as membrane damaging, neurotoxicity, edema and prolongation of coagulation time. Hence the myotoxicity, neurotoxicity and edema induced by this venom are due to the presence of large amount of PLA2.
  • The venom significantly delayed the recalcification time, PT and aPTT. Elapid venoms are anticoagulant in nature due to the presence of large amount of strong and weak anticoagulant PLA2 enzymes. Venom PLA2 enzymes inhibit activation of FX to FXa which leads to disruption in the formation of prothrombinase comples, which is required for blood coagulation. 
  • Sonoclot and Rotem analysis also demonstrated that the Naja Naouthia venom is anticoagulant in nataure. The whole citrated blood analysis by sonoclot clearly indicated the depletion of fibrinogen in the reaction when pre-incubated with venom. 
Polyvalent antivenom is currently used by the medical practitioners for the treatment of snakebite patients in India, prepared from the Big Four, which includes Naja Naja. In most of the cases, it has been observed that the efficacy is highly reduced when antivenoms raised agaisnt venom from a particular geographic region is used to treat victims from another region.
  • The polyvalent antivenom could neutralize some of the biochemical and biological activity at 1:10 ratio (venom:polyvalent antivenom) and complete neutralization was observed when the dose of the polyvalent antivenom was increased by 10 fold. 
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I've found a surprising article too. It is about two cases of Naja Kaouthia bites treated by the Department of Emergency Medicine in collaboration with the Pittsburgh Poison Center, at the Presbyterian Hospital, Pittsburgh, Pennsylvania. People keep them at home, secluded very far away from their natural habitat... and still they are lucky enough to be treated with anti-venom. I do have only the abstract.

Naja kaouthia: Two cases of Asiatic cobra envenomations
Khandelwal et al. 
The Journal of Emergency Medicine
Volume 32, Issue 2, February 2007, 171-174

ABSTRACT:
Envenomation from cobra bites causes major morbidity and mortality in Asia and Africa but rarely in the United States. We describe two patients bitten by the Asiatic Cobra (Naja Kaouthia)—both successfully treated in the emergency department. Patient 1 was a 23-year-old woman bitten in the buttock by her cobra. Examination demonstrated two puncture wounds. She developed cranial neuropathy, respiratory failure, and coagulopathy 10 h later, necessitating endotracheal intubation and polyvalent antivenom administration. The patient recovered fully with minimal wound necrosis. Patient 2, a 44-year-old man, was bitten on the hand by his cobra. Examination revealed a puncture wound with progressive swelling. Edrophonium and monovalent antivenom were administered, and he recovered uneventfully. These cases emphasize the varied clinical presentations of the Asiatic cobra. Patient 1 developed delayed neurotoxicity, respiratory failure, and hematotoxicity with minimal wound necrosis, whereas Patient 2 experienced a more typical clinical course.


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RESOURCE: TOXINOLOGY.COM

This website belongs to THE UNIVERSITY OF ADELAIDE (Australia).
Contains very useful information about venomous animals like snakes, spiders and scorpions.


  • General details
    • Family
    • Subfamily
    • Genus
    • Specie
    • Common names
    • Local names
    • Region
    • Countries
  • Taxonomy and biology
    • Adult length
    • General shape
    • Habitat
    • Habits
    • Prey
  • Venom
    • Description of typo of toxins and if present or not. (Neurotoxic, myotoxic, pro-coagulant... etc.)
  • Clinical effects
    • Dangerousness, rate of envenoming.
    • Description of local and/or systemic effects
  • First Aid
    • General measures for, in this case, Elapid bites.
  • Treatment
    • General snakebite treatment.
    • Key diagnostic features
    • General approach to management
    • Antivenom therapy

  • Available antivenoms. 
It this case, we will know that specific antivenoms for Naja Kaouthia  are available in different countries. 

Is there any study on how these antivenoms (there is even King Cobra, banded krait  and Russell's viper monospecific antivenom!) could be effective in North-East India patients?


This antivenom is specific for Naja Kaouthia, which is the Naja specie prevalent in Thailand.
I wonder what kind of antivenom was given to the two patients of Pennsylvania. The authors specify one was polyvalent and the other was monovalent. 







Here a beautiful set of antivenoms manufactured by de Thai Red Cross Society. 



1. Antivenom Code: SAsTRC02

Manufacturer: Science Division, Thai Red Cross Society
Phone: ++66-2-252-0161 (up to 0164)
Address: Queen Saovabha Memorial Institute
1871 Rama IV Road
Pathumwan
Bangkok 10330
Country: Thailand
Antivenom Name: Cobra Antivenin

2. Antivenom Code: SAsGPO03
Antivenom Name: Cobra Antivenom
Manufacturer: Thai Government Pharmaceutical Organisation
Phone: ++662-644-8851
Address: 75/1 Rama VI Road,
Ratchathewi
Bangkok 10400,
Country: Thailand

3. Antivenom Code: SAsVRU04
Antivenom Name: Naja kaouthia Antivenom
Manufacturer: Venom Research Unit
Address: University of Medicine and Pharmacy
Ho Chi Minh City
217 An Duong Vuong Q5
Country: Vietnam

4. Antivenom Code: SAsPIM01
Antivenom Name: Bivalent
Manufacturer: Pharmaceutical Industries Corporation
Phone: +95-1-566742
+95-1-566750
Address: 192 Kaba Aye Pagoda Road,
Bahan, Yangon,
Country: Myanmar ( Burma )

5. Antivenom Code: SAsPIM02
Antivenom Name: Anti-Cobra, Siamese Cobra
Manufacturer: Pharmaceutical Industries Corporation
Phone: +95-1-566742
+95-1-566750
Address: 192 Kaba Aye Pagoda Road,
Bahan, Yangon,
Country: Myanmar ( Burma )




ॐ लोकाः समस्ताः सुखिनो भवन्तु ॥
Om Lokah Samasthah Sukhino Bhavantu
May all beings everywhere be happy and peaceful.





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