Tuesday 7 February 2017

(V): VSofI: Hypnale hypnale. Sri Lanka polyspecific antivenom pre-clinical results. AVRI



As said in the last post, there is no antivenom available for Hump nosed pit viper (Hypnale Hypnale) envenomation. Good news is that in Sri Lanka, through a collaborative initiative, a polyspecific antivenom has been developed that includes Hypnale hypnale


Toxicon 122, October 2016, pg 152-159
Development of a new polyspecific antivenom for snakebite envenoming in Sri Lanka: Analysis of its preclinical efficacy as compared to a currently available antivenom

Mauren Villalta a, Andre s Sa nchez a, María Herrera a, Maria ngela Vargas a, A lvaro Segura a, Maykel Cerdas a, Ricardo Estrada a, Indika Gawarammana b, Dan E. Keyler c, d,Kimberly McWhorter c, Roy Malleappah c, Alberto Alape-Giro n a, Guillermo Leo n a,
Jose María Gutie rrez a, *a Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San Jos e, Costa Ricab Faculty of Medicine, University of Peradeniya, Sri Lanka
c Animal Venom Research International, Moreno Valley, CA, USA
d Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA 



(You can read full article or download the PDF from Researchgate)

ABSTRACT
A new whole IgG, freeze-dried, polyspecific antivenom was prepared from the plasma of horses immunized with the venoms of the snakes Daboia russelii, Echis carinatus, Hypnale hypnale, and Naja naja from Sri Lanka. The preclinical neutralizing ability of this antivenom against several toxic and enzymatic activities of these four venoms was analyzed, and compared with that of a batch of VINS antivenom (India) being currently used in Sri Lanka. The activities tested were: lethality, hemorrhagic, in vitro coagulant, proteinase and phospholipase A2. Both antivenoms neutralized, to a different extent, these activities of the venom of D. russelii, E. carinatus, and N. naja. In general, the polyspecific Sri Lankan antivenom was more effective than the Indian antivenom in the neutralization of the venoms of D. russelii and E. carinatus, whereas the Indian antivenom showed a higher efficacy against the venom of N. naja. Regarding H. hypnale, the new Sri Lankan antivenom was effective in the neutralization of all activities tested, whereas the Indian antivenom neutralized lethality but not hemorrhagic, coagulant, proteinase and PLA2 activities, in agreement with the fact that this venom is not included in the immunization mixture for this antivenom. Results suggest that the new polyspecific Sri Lankan antivenom has a satisfactory preclinical neutralizing profile and compares favorably with the Indian antivenom. This is ready to be tested in a clinical trial to evaluate its efficacy and safety in human victims of snakebite envenomings by D. russelii, E. carinatus and H. hypnale in Sri Lanka. 


To start with, the study describes the different profiles for the common venomous snakes in Sri Lanka like Daboia russelii, Echis carinatus, Hypnale Hypnale and Naja Naja. As there is no diagnostic tool to determine which is the snake responsible for the biting, a syndromic approach is the most common sense procedure to be followed. The authors describe the results  some wonderful studies done by Ariaratnam et al, 2009, 2008 on that subject. 
In Sri Lanka, the antivenoms used are manufactured in India, from indian snakes. Geographical variations are very important. The main reasons for developing their own antivenom are:
1) The need to use a more geographical congruent antivenom, prepared from the snakes of the territory. 
2) As Hypnale hypnale bites are very common and the possibility of death or chronic disability is now an accepted fact, this snake should be included in the antivenom.
3) A high incidence of adverse reactions with the indian antivenom.

The initiative consist on an international partnership:

  • Animal Venom Research International (AVRI), a nonprofit charity from USA

  • Instituto Clodomiro Picado, a public research and antivenom manufacturing center on the University of Costa Rica

  • University of Peradeniya and other public institutions in Sri Lanka. 


Superb view of Peradeniya University Campus





























The authors built a serpentarium after obtaining all the permits and sample venoms were sent to Instituto Clodomiro Picado for the development of the antivenom. 
After passing all the quality controls common practice in the Instituto Clodomiro Picado, the preclinical efficacy of the antivenom was measured following in-vitro and in-vivo assays based on the effect of the different venoms by themselves and after the incubation with the polyspecific antivenom developed. 
Results were compared to a lot of VINS antivenom (polyspecific antivenom from India against Naja Naja, D. Ruselii, E. Carinatus and B. Caeruleus).

All this is a process that has taken some years to develop and to put into practice. To me this is a very important initiative. It shows how sharing knowledge and resources is possible!



There is a preliminary article:
Toxicon Vol 69, July 2013, pg 90-97
Antivenom for snakebite envenoming in Sri Lanka: The need for geographically specific antivenom and improved efficacy
D.E. Keylera,b,*, I. Gawarammanaa,c, J.M. Gutiérrezd, K.H. Sellahewaa,e, K. McWhorter a, f, R. Malleappah a
a Animal Venom Research International, Moreno Valley, CA, USADepartment of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA c Faculty of Medicine, University of Peradeniya, Sri Lankad Instituto Clodomiro Picado, School of Microbiology, University of Costa Rica, San José, Costa Ricae Department of Medicine, Melaka Manipal Medical College, Malaysiaf School of Public Health, Loma Linda University, Loma Linda, CA, USA
ABSTRACT

Sri Lanka is a tropical developing island nation that endures significant economic and medical burden as a result of snakebite envenomation, having not only a high prevalence of envenomations, but also one of the highest incidence rates (200 snakebites/100,000 people/year) of venomous snakebite in the world (Kasturiratne et al., 2005). Ironically, the very snakes responsible for this human morbidity and mortality are a valuable biomedical and ecological national resource, despite the medical and economic consequences of envenomation. Currently, no snake antivenom is produced using venoms from native Sri Lankan snakes as immunogens, and there is a true need for an efficacious Sri Lanka, poly-specific snake antivenom. An approach to fulfilling this need via combining the scientific, technological and economical resources from Costa Rica and the United States with the knowledge and talent of Sri Lankan official governmental agencies, legal counsels, environmental, medical and veterinary academic institutions, and religious and cultural leaders has been initiated, coordinated and funded by Animal Venom Research International (AVRI), a nonprofit charity. This bridging of nations and the cooperative pooling of their resources represents a potential avenue for antivenom development in a developing country that suffers the consequences of few specific resources for the medical management of venomous snakebite. The desired final outcome of such an endeavor for Sri Lanka is, most importantly, improved medical outcomes for snakebite patients, with enhanced and expanded science and technology relating to snake venoms and antivenoms, and the collateral benefits of reduced economic cost for the country.


You can visit the web of AVRI, see the process, how this initiative started, have a virtual tour on the serpentarium they build, what do they do... very interesting.


http://www.usavri.org

The mission of AVRI is to aid in the development of more effective prevention and treatment protocols for animal envenomation (bites or stings from venomous animals) by mediating between involved parties, educating medical personnel and the public in order to reduce morbidity and mortality around the world.

The technology exists to improve pharmacotherapies, treatment protocols and quality of care, at an affordable cost, within the regions suffering most from animal envenomation. The underserved populations afflicted by animal envenomation are in dire need of external support to champion their cause and AVRI is the organization that can serve as their advocate. 


Furthermore, AVRI emphasizes animal conservation principles, with regard for all local laws, to minimize human/animal conflicts and prevent ecological imbalances. Venomous animals, while potentially harmful to humans, are also the victims of fear, myth and misinformation often leading to their being killed unnecessarily. These animals play an important role in the natural environment and need to be preserved. Through education and awareness, AVRI hopes to dispel fears, prevent harmful conflicts and preserve biodiversity.


Two TED talk on "creating an antivenom for SriLanka" by AVRI 


Published on Jan 30, 2014
TED Talk with Roy Malleappah, executive director of AVRI and Kimberly McWhorter,





Published on Mar 8, 2012
YOUTH TED talk by Kimberly McWhorter
Associate Executive Director, Kimberly McWhorter, MPH, CPH, DrPH(c) Board Certified in Public Health by the National Board of Public Health Examiners; Program Coordinator/Educator for Riverside County, California Community Health Agency; Program Planner; Grant writer; Recipient California State Association of Counties Merit Award for creation and implementation of an innovative local government program.



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

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