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VENOMOUS SNAKES OF VENOMOUS SNAKES OF MEDICAL IMPORTANCE &MEDICAL IMPORTANCE &

SNAKE BITES SNAKE BITES MANAGEMENT IN VIETNAMMANAGEMENT IN VIETNAM

Trinh Trinh XuanXuan KiemKiem, Trinh Kim , Trinh Kim AnhAnh, Le , Le KhacKhac QuyenQuyen, Nguyen Ba , Nguyen Ba PhuocPhuoc, , Thai Thai DanhDanh TuyenTuyen, Trinh , Trinh XuanXuan Long, Pham Long, Pham ManhManh Hung, David Hung, David A. A. WarrellWarrell, at al., at al.

INTRODUCTIONINTRODUCTION

For centuries, there have been of snake bites patients with an associated with

high morbidity and mortality, particularly in tropical countries such as Vietnam.

However, this medical problem has been neglected.

.

100 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 1990.

BEFORE 1990BEFORE 1990

There are # 30,000 cases of bites/year. Most snake bite victims were treated by non specific methods, which were

t t d i l t th t diti l h lentrusted mainly to the traditional healers

- Mortality: 19.8 % (Severe envenoming)

- Amputation: 11%

- Deformity: 14 %

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METHODSMETHODS

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.

.

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RESULTSRESULTS: : 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. 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.

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Hình Đẻn cơm (Lapemis hardwickii)

68%

18 - 55 Y/O (1164)

RESULTS 2.-Epidemiology

2.1.-Snake bite patients according to age distribution at Cho Ray hospital, HCM City, (1990-1996) (n: 1.709)

8%

24%

(132)>55 Y/O

(413)

<18 Y/O

69%

Male

(1184)

RESULTS: 2.2.- Snake bite patients according to sex distribution in CR hospital (1990-1996) (n= 1.709)

31%

Female

(525)

Farmers

45% (769)Other

27%(461)

RESULTS 2.3.- Occupations of snake bite patients /C.R hospital (1990 -1996) (n=1.709 cases)

Children 20% (342)Snake dealers

5% (86)

Rubber plantation workers 3% (51)

Envenoming (n=1.128) (66%)

RESULTS 2.4.- Snake bite patients according to envenoming & non envenoming-CR hospital (1990-1996)

(n= 1.709)

Non envenoming (n=581) (34%)

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T. albolabris

43,3% (865)N. kaouthia

C. rhodostoma19,04% (388)

RESULTS 2.5.- Data showing proportion of individual snake bites CR hospital (1990 – 1998) (n =1.997)

27,5% (549)

N.siamensis

6,3% (125)B. Candidus

2,1% (42)O. Hannah

1,2% (24)

Sea snake

0,2% (4)

RESULTS: 3.-Two major Two major syndromes syndromes of envenomingof envenoming

1.- Neurotoxicity

2.- Bleeding & Coagulation disorders with DIC & Acute Fibrinolysis

.

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Principal of AV production –F(ab’)2

F(ab)2

PRESENT

PEPSIN

Fc PORTION Fc PORTION

F(ab)F(ab)FUTURE

Principal of AV production (Fab)

Fc PORTIONFc PORTION

PAPAIN PAPAIN

IgG MOLECULE

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BC F(ab')2 AV confirmation by SDS-PAGE

F(ab)'2

After

purification

-----------------------

IgG before purification

RESULTS: 4.-

5 5 types of types of AVs AVs have have producedproduced in VN:in VN:

1- Naja (kaouthia+atra)

2 Ophiophagus Hannah (black+yellow)2-Ophiophagus Hannah (black+yellow)

3-Bungarus (candidus+multicinctus)

4-Trimeresurus albolabris

5-Calloselasma rhodostoma

RESULTS: 5.- Clinical Clinical applicationsapplications

5.1.- More than 3,000 snake bite patients were treated AVs to give a good response: Safety & Efficacy.

5.2.- 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:AV reactions:

1) -Early reactions:

- Anaphylactic shock (2.3%).

- Pyrogenic reaction (15.2%)

2) -Late reaction (serum sickness type) < 1 %.

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42

58 59

42

58

30

40

50

60

Comparison of clinical efficacy between two groups (a) and (b) at Cho Ray Hospital

1114

8

13 1410

14

1,8%

22%

0

10

20

30

Admission N. Eye

muscle

Ar. V

ceased.

Mus

power

Osermann Glasgow Mortality

Group (a): NKAV (54P)

Group (b): Non NKAV (9P)

P<(0,001)

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314

417

529

400

500

600

700

800

900

v ic t ims

number o f sna c k bi t e v ic t ims a t Ch o Ra y

Ho spi t a l in so ut h er n Vie t Na m f r o m 1976 t o 1996

0 0 4 11 6 9 11 39

67

71

128

151

71

68

103

216299

358

0

100

200

300

400

1976 85 87 89 91 93 95

Envenoming victims Non – envenoming victims

80 86 88 90 92 94 96

STRATEGY OF SCIENTIFIC RESEARCHSTRATEGY OF SCIENTIFIC RESEARCH

The scientific research collaboration between The scientific research collaboration between VN VN –– USC (U.S) to make a new candidate drug USC (U.S) to make a new candidate drug from snake venom for cancer treatment in VN.from snake venom for cancer treatment in VN.

Since 2001, the project has been started. Since 2001, the project has been started. p jp jIt was approved by VN Government in 2013.It was approved by VN Government in 2013.The first result: These The first result: These DisintegrinsDisintegrins from from CR CR were found with a good biological function to were found with a good biological function to

anti cancer cells & tumors. anti cancer cells & tumors. Recombinant Recombinant DisintegrinsDisintegrins & Nano technology & Nano technology will be applied for making an Antiwill be applied for making an Anti--cancer drug. cancer drug.

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A group of top government science andtechnology officials from Vietnam visited USCon Sept.17,2013 and meeting with researchers.Frank Markland Ph.D., professor ofbiochemistry and molecular biology hosted thevisit, which also featured discussion of hiscollaboration with researchers at the Researchcollaboration with researchers at the ResearchInstitute for Rural Technology and Hai PhongMedical University both in Vietnam. Theirresearch seeks ways to use snake venompeptides as chemical weapons against breastand prostate cancers.

CONCLUSIONCONCLUSION1) 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 forproduced to have a good safety, efficacy & permitted for use since 1998. 4) 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.