11/23/2013. However, this medical problem has been neglected..

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1 VENOMOUS SNAKES OF MEDICAL IMPORTANCE & SNAKE BITES MANAGEMENT IN VIETNAM INTRODUCTION For centuries, there have been of snake bites patients with an associated with high morbidity and mortality, particularly in tropical countries such as Vietnam. Trinh Xuan Kiem, Trinh Kim Anh, Le Khac Quyen, Nguyen Ba Phuoc, Thai Danh Tuyen, Trinh Xuan Long, Pham Manh Hung, David A. Warrell, at al. However, this medical problem has been neglected years ago, in Saigon Pasteur Insti, Dr. Calmette was the first Dr in the World to research Cobra AV & applied for 02 patients successfully. WHO, 1971: AV has been the most effective form & widely used for snake bite treatments in the World. But no AV developed in VN until BEFORE 1990 There are # 30,000 cases of bites/year. Most snake bite victims were treated by non specific methods, which were entrusted t mainly to the traditional healers - Mortality: 19.8 % (Severe envenoming) - Amputation: 11% - Deformity: 14 % 1

2 METHODS 1.-Epidemiology of snakebites & identification of snakes by Alberdin & Oxford Universities. (Wuster, D.Warrell) 2.- A.V production, Q.C & clinical trial courses: WHO guidelines, D.Theakston, D.Warrell.. 2

3 RESULTS: 1) IDENTIFICATION: SNAKES OF MEDICAL IMPORTANCE IN VN 2 main families of venomous snakes,10 species characterized for each geographical area, land snakes & sea snakes in VN. * Elapidae: 1.- Naja kaouthia / South West. 2.- Naja atra / North 3.- Naja siamensis / South East. 4.- Ophiophagus hannah : (black / Middle & yellow / South West) 5.- Bungagus fasciatus/ every where. 6.- Bungarus candidus / South 7.- Bungarus multicinctus / North 8.- Hydrophidae (Sea snakes) concentrated in Phan Thiet (Middle) Sea. *Viperidae: 9.- Trimeresurus albolabris / every where 10.- Calloselasma rhodostoma / South East. 3

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5 Hình Đẻn cơm (Lapemishardwickii) RESULTS 2.-Epidemiology 2.1.-Snake bite patients according to age distribution at Cho Ray hospital, HCM City, ( ) (n: 1.709) RESULTS: Snake bite patients according to sex distribution in CR hospital ( ) (n= 1.709) Y/O 68% (1164) Male (1184) 69% 8% (132) >55 Y/O 24% (413) <18 Y/O Female 31% (525) RESULTS Occupations of snake bite patients /C.R hospital ( ) (n=1.709 cases) RESULTS Snake bite patients according to envenoming & non envenoming-cr hospital ( ) (n= 1.709) Other 27%(461) Farmers 45% (769) Envenoming (n=1.128) (66%) Rubber plantation workers 3% (51) Snake dealers 5% (86) Children 20% (342) Non envenoming (n=581) (34%) 5

6 RESULTS Data showing proportion of individual snake bites CR hospital ( ) (n =1.997) T. albolabris 43,3% (865) Sea snake 0,2% (4) O. Hannah 1,2% (24) C. rhodostoma 19,04% (388) B. Candidus 2,1% (42) N. kaouthia 27,5% (549) N.siamensis 6,3% (125) RESULTS: 3.- Two major syndromes of envenoming 1.- Neurotoxicity 2.- Bleeding & Coagulation disorders with DIC & Acute Fibrinolysis. 6

7 Principal of AV production F(ab ) 2 Principal of AV production (Fab) PRESENT FUTURE F(ab) F(ab) F(ab) 2 PEPSIN PAPAIN PAPAIN Fc PORTION Fc PORTION Fc PORTION Fc PORTION IgG MOLECULE 7

8 BC F(ab') 2 AV confirmation by SDS-PAGE F(ab)' 2 After purification IgG before purification RESULTS: types of AVs have produced in VN: 1- Naja (kaouthia+atra) 2-Ophiophagus Hannah (black+yellow) 3-Bungarus (candidus+multicinctus) 4-Trimeresurus albolabris 5-Calloselasma rhodostoma RESULTS: 5.- Clinical applications More than 3,000 snake bite patients were treated AVs to give a good response: Safety & Efficacy Comparative study with group counterpart, but not AVs available for treatment before: * Reduced the mortality from 19.8 % to 1.5 %. * Reduced amputation from 11% to 1%. * Reduced permanent deformity from 14% to 5%. * Reduced the mean time for recovering completely from 45 days to 72 hrs. AV reactions: 1) -Early reactions: - Anaphylactic shock (2.3%). - Pyrogenic reaction (15.2%) 2) -Late reaction (serum sickness type) < 1 %. 8

9 Comparison of clinical efficacy between two groups (a) and (b) at Cho Ray Hospital % Admission Group (a): NKAV (54P) P<(0,001) N. Eye Ar. V muscle ceased Mus Osermann Glasgow Mortality power 1,8% Group (b): Non NKAV (9P) 9

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11 number of snackbit e vict ims at Cho Ray Ho spi t a l i n so ut h e r n Vi e t Na m f r o m 1976 t o 1996 STRATEGY OF SCIENTIFIC RESEARCH vict ims Envenoming victims Non envenoming victims The scientific research collaboration between VN USC (U.S) to make a new candidate drug from snake venom for cancer treatment in VN. Since 2001, the project has been started. It was approved by VN Government in The first result: These Disintegrins from CR were found with a good biological function to anti cancer cells & tumors. Recombinant Disintegrins & Nano technology will be applied for making an Anti-cancer drug. 11

12 A group of top government science and technology officials from Vietnam visited USC on Sept.17,2013 and meeting with researchers. Frank Markland Ph.D., professor of biochemistry and molecular biology hosted the visit, which also featured discussion of his collaboration with researchers at the Research Institute for Rural Technology and Hai Phong Medical University both in Vietnam. Their research seeks ways to use snake venom peptides as chemical weapons against breast and prostate cancers. CONCLUSION 1) The venomous snakes of medical importance & epidemiology of snakebites in VN were identified: 2 families & 10 species # 30,000 cases of bites/ year. 2) Two envenomed syndromes characterized for each: Neurotoxicity & Coagulation Disorders (DIC-Fibrinolysis) 3) 5 main kinds of AVs have been researched & produced to have a good safety, efficacy & permitted for use since ) The scientific research collaboration between VN- USC to find a new candidate drug for cancer treatment has been establishing & performing well. (1): PCC of Bach Mai hospital, Hanoi., Vietnam. (2): Cho Ray hospital, Ho Chi Minh City, Vietnam. (3): The University of Oxford, Nuffield Department of Clinical Medicine. 12