Snake Bite: Approach to a case in Endemic region

Major (Dr) Ashutosh Ojha & Colonel (Dr) Sharat Johri Snake has been an object of worship since time immemorial. It was probably due to fear or respect. In Hindu mythology, Lord Vishnu is shown as lying over many headed Cobra called Sheshnag and Lord Shiva has Cobra coiled round his neck. Old Egyptian nobilities are shown with cobrahood around their forehead. Jews and Central Americans also have their ways to remember these species. Even many medieval emblems have snakes as an essential symbol. Many cultures have an auspicious day especially reserved for worshipping snakes. Nagpanchami is celebrated worshipping cobra. Almost in all continents there are pockets where snake bites are accepted ,as a curse from some unholy spirit and people go for spiritual cure rather than seeking urgent medical attention.

Epidemiology : There is very little reliable information on incidence of snake bites in many parts of the world.

In India available published literature suggests yearly 15000 to 20000 of deaths due to snake bites. This data is based on the death registered in the states where snake bite cases are common. As per WHO bullentien, there are 5.6 to 12.6 deaths per 10000 populations in the endemic region. [ 1]

Snake bite cases cluster around the time, when there is heavy rains, floods, deforestation, and sudden movement of large population due to any reason. Myanmar has probably highest mortality figure in Asia due to snake bite. In India, Maharashtra records the highest number of snake bites followed by West Bengal, Tamilnadu, Uttar Pradesh and Kerela. In Maharashtra 70 bites per 100000 populations occurs yearly with 2.4 per lakh mortality .[2] In Rajasthan, Marwar and Mewar region and Jammu region of Jammu and Kashmir have large number of viper bite and have significant mortality.

Most case report during rains and floods, there is high evidence of cases in mobile population such as troop bodies going for exercise, newly established camps of laborers of border roads, paramilitary forces which camp in previously unoccupied buildings. Mostly bites occur between midnight and 0400 hrs, usual site of bite is lower limb probably due to inadvertent trodden snake. In India, more than 2/3rd of bites are due to viper and 1/4th due to Russel viper and still smaller number due to kraits and cobra .

There have been a number of publications, suggesting haemotoxic viperine bites far out number neurotoxic snake bites though almost all refer to local epidemiology. However ,in coastal areas, sea snake bite is usually on upper limbs with severe local manifestation in fisherman.

For correct epidemiology studies. ELISA (Enzyme Linked Immunosorbent Assay) to identify antigen and antibody is required; this technique can have reliable identification and sensitive quantification of venom antigen and antibody.

Natural antibody is detectable in serum by one week of bite, which rises and peaks over in one year and remains detectable for as long as 3 yrs. A few studies are under way but the reports will take time to guide us.

In India 216 species of snakes are reported, out of which 56 are reported poisonous.

Identification of poisonous snakes1) Fangs; It is most distinctive feature of poisonous snakes this is hollow and

grooved modified teeth in upper jaw in communication with salivary glands. In elapidae (cobra & kraits) and sea snakes they are short & immobile, while in viperadae, they are large, curved and have large range of movements.

2) Scales on Belly: In poisonous snakes, belly scales are large and extend across the belly.

3) Head: Vipers have heavy triangular head with small scales all over, There may be a pit, located between nostril and eye, in case of pit viper.In elapidae, there are large head scales. In cobra, upper third labial is largest and touches the eye and nasal shield. In kraits, lower 4th labial scale is largest. In poisonous sea snakes, there are large head scales and valved nostrils.

4) Pupil: Poisonous snake have generally elliptical; and vertical slit pupil.Although mostly killed snakes have smashed head. Still, if we can get one side undeformed eye in killed snake, it can aid in identification.

5) Body design: Kraits have central row of almost hexagonal scales. It also has white and black stripes, across the bodies. Some cobras have spectacle like mark on their hood.

6) Fang marks on the victim’s body: In non poisonous snake bite, bite marks is stretched with multiple indentation.

In poisonous snake bite easy identification of different snakes Cobra- Hood may be present while alive, large scale on head, pupil is round ,upper 3rd labial touches eye and nostril, large belly scales are across the width. Krait -4th Lower labial in undersurface of mouth is largest, hexagonal scales in central row on the belly, body may be banded.Viper -Triangular heavy head with small scales all over, large belly scales extended across the width.

Snake venom: brief chemistry It is a complex mixture of enzymes, non enzymes peptide toxin and non toxin proteins, including heavy metals. It is acidic as well as basic (pH-4.6 to 10). There are over 20 different types of enzymes viz. phospholipids A2, B, C, D, hydrolases, phosphatases proteases, nucleotidases, ATPases, hyaluronidases and others. There are many species of snake whose venoms is yet to be analyzed. Based upon the proportion of the toxins, the venom is vasculotoxic neurotoxic or both. The molecular weight of venom varies from 1500 Dalton to 30 kilo Dalton. Light venom viz.of viper venom is easily absorbed in blood and has more systemic effect while heavy venom viz. sea snake has more of local effect. [4]

Constituents of venomEnzymes : Phospholipids A Hyaluronidase Exo-peptidases L-amino-oxidases Phosphatases Exo-Nucleases Acetyl choline esterasesToxins: Nerve Growth Factor Hemorrhagins Neurotoxins CardiotoxinHeavy metals: Lead Mercury

A study done in Africa has shown that venom constituents vary with season, age of the snake and periodicity of bite.Lethal dose of venomCobra 120mgKrait 60 mgViper saw scaled & Russell 150mg

Onset of pathophysiological effects takes place from 1 hr to 7 hrs.Neurotoxic & local reaction precedes the coagulopathy.Excreation: Venom is excreted by renal route.Detection of venom & quantitative assessment of venom can be done by ELISA which is mostly of academic interestPathophysiology of snakes envenomationLocal swelling: More common in viper and sea snakes, it starts within minutes and massive swelling may take place in 48 – 72 hrs, mostly hemorrhagins and hydrolases open endothelial pores resulting in leakage of plasma and whole blood. It may lead to hypovolomic shock, compartment syndrome and its consequent long term sequaelae. Local necrosis: Due to cytolytic enzymes present in venom, local necrosis of tissue takes place. In cobra bite, necrosis appears early. It is associated with local swelling, mimics wet gangrene Early non specific symptoms: Vomiting, diarrhea, headache, abdominal pain may occur. Some patients collapse. These symptoms are possibly kinin mediated and resolve after an hour by activation of bradykinin system. In viper bite, the local necrosis occurs late in due to ischemia around 2 to 3 weeks later and is like dry gangrene [9].

Shock: It may occur due to anaphylaxis with the venom. It may take place due to extensive volume leak from vessels in case of viper bite.Pulmonary intravascular clotting, pulmonary edema and cardiac depression may be a contributory factor. Spontaneous Heamorhage: It is common amongst viper bite even days after the bite. It may occur from any of the orifice viz. Epistaxsis, haematemesis, haemoptysis, haematuria, malaena, haematochesia and even heavy periods.There may be some life threatening complication such an intracranial hemorrhage. It can take place despite giving adequate doses of ASV and may take place after as late as 3 weeks.Effects on circulation: There is leukocytosis of polymorphonuclear type. In some viperine bites, these is pocoagulant state due to activation of prothrombin to thrombin and fibrinogen to fibrin. It must be understood that bleeding in viperine bite does not take place due to coagulation dysturbance but due to haemorrhogins present in venom. In sea snakes as well, the hemorrhagic manifestations are quite common [9]Renal failure; Renal failure is common complication of viper bite. It is fairly common common and due to varied renal pathology, It is most commonly implicated cause of death[6]. It can take place within 6 hr of bite to as late as 4 to 5 years as chronic glomerulonephritis, as per a report, the pathology demonstrated are as follows microscopic.Microscopic Pathology

a) Acute Tubular Necrosis

b) Acute cortical necrosis

Percentage50- 70%

20-25%

Onset6 hrs to 72 hrs

12 to 72hrs

Mesengsal proliferation and basement membrane thickening leading to nephrotic syndrome and late renal failure are reported frequently in different case reports.Chronic glomernlonephritis and delayed renal failure is reported in viper and sea snakes.Renal complications are probably due to shock, myoglobinaemia, haemoglobinuria haemolysis, sepsis and disseminated intravascular coagulopathy. Many authors have suspected hypersensitivity to venom as a cuse to renal failure [5].Neurotoxic effects: Elapidae(Cobra & Krait)and sea snake venom cause neurotoxic effect due to nemomuscualar blockade commonly affected muscle groups are of eye, tongue, throat, chest (respiratory muscle leading to respiratory paralyses).Neurotoxins are small molecular weight compounds which are excretable through kidneys. They have less antigenicity. Cobra toxin causes N.M. - blockade of postsynaptic type without decrease of acetylcholine and responds well to Inj Neostigmine.Krait venom has neurotoxicity of presynaptic type. It remains sensitive to Acetyl choline hence response to Inj Neostigmine is less satisfactory.Besides acute, life threatening respiratory paralysis, venom also causes sensory motor type of polyneuropathy, as delayed complication. It rarely causes altered sensorium. Hence, if a snake bite case has alterred sensonium, an alternative cause should be looked for.

Cardio toxic Effect: - Cobra venom is known to cause paralysis of cardiac muscle causing asystole. Hyperkalaemia after massive haemolysis causes depressed cardiac function.

Mytoxic effect: Sea snakes are known to cause myotoxic effect, cause rhabdomyolysis and hyperkalaemia causing threat to life.

Clinical features: Snakes are timid creatures .The bite is usually defensive rather offensive. Hence, usually, the patient is male of young age group, mobile, probably has performed manual labor involving cultivation or any economic activity in which he has caused displacement of habitat of snakes. Mostly site of bite is in lower limb. It may be any part of body in contact with floor. However, sea snakes bite on the hands of the fishermen.

Patient is usually in terror which may cause nausea, vomiting, dizziness diarrhea syncope, tachycacardia, cold calm skin, sweating, numbness and difficulty in swallowing and respiration.The hyper activity of autonomic nervous system maybe a manifestation of envenomation . There is local pain at the site of bite, which is followed by swelling cellulitis , ecchymosis, edema and lymphangitis.

Haemotoxic syndrome: Local pain, progressive swelling, bruising ,lymphangitis bleeding from the wound are the usual manifestation. Patient may have blistering ,necrosis over the next few days. He may have compartment syndrome leading to neuro- vascular compromise.

Earliest & almost diagnostic symptoms of haemotoxic syndrome are haemorrhagic blebs with uncontrolled bleeding from the site. Epistaxis haematemesis, ecchymosis haemoptysis, subconjuctival, retroperitoneal & intracranial bleeding is frequently seen. Large echymosis, purpura, gangrene of lips, toes and fingers are also frequently seen.

Massive extravasations of intravascular fluid may lead to hypotension, tachycardia, tachyopnoea, respiratory distress and shock. Renal failure may result from hypotension and direct nephrotoxic effect of snake venom.

Direct myocardial depression is noted as reduced inotropic function. Electrocardiography changes such as ST/T depression and elevation ,1st or 2nd degree heart blocks and hyperkaleamia is frequently seen in complicated cases. Involvement of anterior pituitary leading to Sheehan’s syndromes is reported.

Neurotoxic Syndrome: Elapid venom is more neurotoxic, symptoms may appear within 20 minutes of bite & may be as delayed as 24 hours. In acute stage, cranial nerve involvement, respiratory muscle involvment takes place. Delayed complication such as sensorymotor neuropathy is seen.

Investigation In haemotoxic syndrome-Hemoglobin may rise due to extravasations of plasma

thereafter anaemia due to bleeding and heamolysis.Polymorphonuclear type of leukocytosis associated with thrombocytopenia is common. Peripheral blood smear shows broken RBC. Clotting time is often prolonged. It is performed as bedside test showing severity of envenomation and response to therapy . Rhabdomyolysis is associated with rise in creatinine kinase, myoglobins, potassium and transaminases. Blood urea and serum creatinine may rise.

Plasma may be pink suggestive of gross haemoglobinaemia. Arterial blood gases, though not done routinely, but may show low bicarbonate level, showing associated metabolic acidosis. Urine is examined for RBCs, hemoglobin, myoglobin and proteins.

ECG is done to look for tachycardia - bradycradia, ST/T changes, AV-blocks, and hyperkalaemia. Chest X-Ray is done to look for pulmonary oedema. Clotting time, Hemoglobin and urine microscopy is done frequently for therapeutic assessment.. It is learnt from experience that clotting time on day one should be done 4 hrly, next day 6 hrly and then after 12 hrly.

Commercial kits for detection of specific snake venom are available, but are costly. ELISA and Radio immune assay can be done but are impractical in our setting.

Though for epidemiological purpose, some studies are underway .

MANAGEMENT OF SNAKE BITE

First aid

After a bite from any reptile, the patient should be immediately removed from the striking distance to avoid repeated bite. Handling of a live snake for the sake of identification should be avoided. Patient should be reassured to treat fight reaction. The site of bite should be wiped, cleaned with water and antiseptic without much handling of the part. Wound should not be incised, excised & sucked and manipulated as it may aid in absorption of venom, introduce infection and damage tissue muscle nerve and vessel. Immobilized the injured part in functional position. Tourniquets may be applied loosely, as these prevent early absorption of venom. It should be removed after giving the initial dose of ASV at the medical centre.

TRANSFER TO NEAREST MEDICAL CENTRE.

Patient should be transferred to a medical centre in outmost comfort without frequent, undue handling. Patient should not be allowed to move unnecessarily as muscle contraction causes absorption of venom early. During transit, hypovolumic shock should be looked for and enough IV fluid should be infused enroute. Syncope and other autonomic symptoms should be treated with 0.5ml of Inj Adrenallin 1:1000 injections with an antihistaminic viz. Chlophenaramin and Promethazin. Clean airway and proper ventilation, enroute helps in early recovery.

AT MEDICAL CENTRE

A large number of bites are dry bite. The patients must be reassured .Quick clinical assessment and early institution of Antisnake venom is the mainstay of the therapy.All the patient of unknown bite must be admitted and observed as on following lines.

(1) Pulse, BP and Respiratory rate.

(2) Size, surface & circumference of local swelling.

(3) Abnormal bleeding from the site of bite, mucosal membranes viz subconjunctival, mucosal surface & injection site.

(4) Base line investigation as advised above.

(5) Naked eye examination of urine.

(6) Single breath count, pulses, pharyngeal muscle function assessment.

Snake bite severity score to evaluate haemotoxic envenomation as suggested by Dart and Hurlburt is basically for African snakes. It is time consuming and is grossly laboratory dependent.

Antisnake Venom (ASV) : It is only specific antidote available for envenomation. Though it is often reported to have sides effects as anaphylaxis, but benefits of ASV far outweigh the risk. It can be given anytime when signs of envenomation come up. In neurotoxic bite cases has been proved beneficial unto 2 days while in haemotoxic it can be given even three weeks after viperine bite.

Availability- From Haffkine Biopharmaceuticals and Serum institute is available usually at 10 ml vial. It is available in Lyophilized form requiring reconstitution. It has potency of 5 years.

Reconstitution: This dry powder requires dissolving in distil water or normal saline. This should be dissolved by side to side shaking and rolling on a hard surface. During vigorous shaking, it may form froth in which ASV powder may get trapped and patient may be given a low potency drug as ASV is trapped in froth, which is left in the bottle.

Indication of ASV

As ASV carries risk of adverse reaction, it should be started when specifically indicated commonly accepted indication are follows.

Haemostatic abnormalities a high coagulation time, rising CT, Thromlaocytopenia, overt bleeding.

Neurotoxicity -Ptosis: Pharyngeal muscle weakness respiratoy muscle involvement.

Hypotension, shock, clinical and radiological evidence of CVS dysfunction.

Acute Renal failure, rising urea, creatinine

Rhabdomyolysis

Lab investigations viz. EISA/RIA positivity

Indication of ASV (Contd)

In suspected cases of snake bite

Rapidly progressive, local swelling with enlayed tender lymphnodes in endemic region.

The above indication may be seen exhaustive but not complete. Bhatt et al have used ASV in unconscious patients brought to causality with statistically significant recovery, proving hypothesis of painless krait bite in Jammu region.

Sensitivity testing: It is done by 0.1 ml of reconstituted ASV injected intradermal and local instillation of diluted ASV in conjunctival sac. Sensitivity testing does not reliably exclude the possibility of early or late reaction. But in severe sensitivity reaction, ASV therapy should be given slowly and under cover of steroid and antihistamine drugs.

Dose of ASV

Dose varies, usually published articles have suggested doses of ASV to start with .The total requirement of ASV, depends upon amount of venom instilled in bite, age of snake and species of the snake bitten. It may vary anything between 100ml to 1500 ml as reported in case reports.However to start with the dose is to be considered as follows.

(a) Progressive local swelling – 50ml

(b) Mild to Moderate – 100 – 150ml

(c) Severe - 150- 200ml

Published studies on dose and protocol

YEAR STUDY PROTOCOL AVERAGE ASV REQD.

1974 BHATT (JAMMU) INTERMITTENT BOLUS 80-270 ML

1985 THOMAS & JACOB (KERALA) CONTINUOUS INFUSION 160ML

1999 TARIANG (VELLORE) CONTINUOUS IV. INFUSION 47-89ML

2000 VIJETH (PONDICHERY) INTERMITTENT BOLUS 179.2ML

2004 SRIMANNARAYAN CONTINUOUS IV 179ML

It is noted that continuous infusion is safer, requirement of ASV is lower and can be monitored more effectively. ASV starts neutralizing the venom immediately and takes care of all circulating venom in 3-4 hrs, but the systemic envenomation may recur hours or days after an initial response. Hence, it is advisable to give last dose of ASV 24 hrs after normalization to prevent recurrence.

Indesprate situations, where IV access in not there, it can be given intramuscular. This route has multiple disadvantages such as erratic absorption, multiple injection and large doses of ASV is required and risk of haematoma formation. It is worth mention that pediatric cases are given in same doses ASV as adult. There is a case report of chronic osteomylitis following administration of ASV intraosseous.

Our Experience

We are presently posted to two large army hospitals around Jammu region ,have managed more than 60 cases of poisonous snake bite, 27 cases were having neurotoxic variety brought to hospital in respiratory paralysis state. They were having bite marks without much of local reaction, we believe that mostly were of krait bite. They required mechanical ventilation for average 18 hrs. Average ASV requirement in our cases was 240ml. None of the case was exhibited with Inj Neostigmine and Atropine.32 cases were having essentially haemotoxic type of presentation, the average ASV requirement was 370 ml over 3 days of ASV therapy.

One case had both neurotoxic and haemotoxic both types of derangements. The total ASV given was 250 ml over 4 days.

Supportive care

Hydration: All the cases were given liberal IV infusing, normal saline was given at @ 150ml/hr and renal output was maintained at 50 ml / hr. After adequate urine output is noted potassium containing fluids may be started.

NEUROTOXIC ENVENOMATION

A clear airway is must during transport from accident site. If respiratory distress occurs, immediately endotracheal entubation and mechanical ventilation be provided. In our experience, most of the victims have been young average age – 36 yrs, required ventilatory support on average for 20 hrs. There are reports that patients required ventilator support for as long as 3 weeks. Incases of cobra bite, Inj Neostigmine 0.5mg along with inj Atropine 0.6 mg IV every half hour for five doses and then after 4 hrly till full recovery is seen should be given. In cases of cobra bite, usually there are local reaction along with neuroparalytic effect while in Kraits usually ,there is no local reaction . It may be a clinical clue for the use Inj Neostigmin . Cobra bite is more common in western region and north east.

GASTO INTESTINAL PROTECTION

Snake bite patients are in inflammatory and in catabolic state. They require early alimentation as it protects gastric mucosa. Ryle’s tube feeding in entubated patients should be given with high calorie liquid meals. Soft bland frequent diets should be provided to the patients who can take orally. Inj Ranitidine should be given to all envenomated patients. Stress ulcers due to hypotension, hyperacidity due to steroid can be prevented.

Renal protection: Frequent urine examination and urine output hourly monitoring can detect early renal dysfunction. Fluid, Inj Frusemide; Inj Dopamine should be given as acute renal dysfunction noted. Usually accepted indications for haemodialysis and peritoneal dialysis hold good for snake bite cases. In viperine bites, the renal dys function is more common, heparin free dialysis is advocated by some as bleeding is common complication .

In our series, 04 cases had renal dysfunction, which required management by nephrologists. Three cases responded to conservative management with intravenous fluid, Inj Dopamine & Inj Furosemide ,one case required haemodialysis and also progressed to chronic renal failure over one year, renal biopsy showed chronicglomerulonephritis.

Treatment of local complications

Snake saliva is a rich source of both aerobic and anaerobic organism; hence broad spectrum antibiotics covering Gram positive, negative and anaerobic organism were given to all our patients. Inj Cefotoxime, Amikacin & Metronidazol were given to the all patients. Dose modification of antibiotics was done as per creatinine clearance.

Local necrosis, compartmental syndrome and local infection at bite site should be managed surgically. In our series, 02 cases had local necrosis, dibribement was done which progressed to non healing ulcer and plastic surgery was done after 6 months. In case of spat of venom in eyes, it should be irrigated thoroughly with water, topical instillation of Atropine, and antibiotics is advisable. Myoglobinuria and haemoglobinuria require correction of hypovolumia, acidosis and mannitol infusion.

Ovine and avian antivenoms are undertrial. Anti snake vaccine also is in experimental stage.

Conclusion;

Snake bite is commonly encountered medical emergency in our clinical practice. It is often incompletely treated. Ancillary management is not done properly. Hence, there is often poor outcome . In our experience, ancillary management along with ASV therapy improves the outcome.

Profile of snake bite cases in our series

Total : 60 cases

Haemotoxic – 32

Neurotoxic without local reaction – 27

Both manifestation – 01

Age Min.-13 years Average 34 years

Max- 56 year

Gender Male 51

Female 09

Hospital Stay Min. 6 days

Max 28 days Average 12 days

Average Total Venom Required -240ml in Neurotoxic cases

-370ml in Haemotoxic cases

Average requirement of ventilator Support- 20 hours

Complications

Local

Necrosis – 02 patients

Severe Oedema with compartmentSyndrome : 04

Systemic

Renal dysfunction: 04[Conservative therapy – 03; Heamodialysis: 01 with progress to chronic glomerular disease.]

References

1. Chapeaux J.P. snake bites: appraisal of global situation,Bull WHO 1998; 76(5); 515-524.

2. Gaitonde BB, Bhattacharya S. An epidemiological survey of snake bite cases in India ;Snake 1980; 12; 129-33

3. Bhatt R.N. Viperine snake bite poisoning in Jammu – J. India Medical Association 1974; 63; 383-392.

4. Anurbach P.S.,Norris R.L. Disorder caused by reptile bite, In Harrison’s principles of Internal Medicine – Eds Kasper, Braunwald Fauci, Hauser, Longo, Jameson 16th Ed. Mc Grow Hills New York 2005, 2593-94

5. Sakhuja V, Chugh K.S., Editorial, J. Assoc Physicians India 1989;37;423-24

6. Merchant MR, Khanna UB, Almedia AF, Acharya V.N., Mittal BV:Clinicopathological study of acute renal failure after viperine bite

7. Kalra SP, Verma P.P, Chatterjee RS. Experience with viperine envenomation MJAFI; 1998 54:204-207.

8. Swaminarayan J; Dutta T.K., Sahai A; Rational use of Anti snake venom; Trail of various resinous in haenotoxic snake envenomtion;J.Ass. Physician India 2004;52;788-793.

9 .Mehta S.R;hashindra V.K. chemical features and management of snake bite, MJAFI; 2002 & 58; 247-249.

10. Virmavi S.K. Dutt O.P. Snake bites in Jammu region :J. India Med Assoc 1987; 85; 132-135.

Brief biodata of authors

Major (Dr) Ashutosh Ojha

MBBS,MD(Medicine)

Presently working as Medical Specialist in Indian Army near Jammu

Interests – Tropical Medicine,

Diabetic Autonomic Neuropathy,

High Altitude Medical Problems(,Dyslipidemia& Hypertension)

Publication s- Pancreatitis; physician perspective-Apr2006

Probiotics in clinical practice-Apr 2006

Drowning –API Textbook of Medicine (Co Author) submitted for 7 th edition

Colonel (Dr) Sharat Johri

MBBS,MD(Medicine),DM(Neurology)

Presently senior adviser in medicine and neurology near Jammu

Previously Professor of Medicine &Neurology AFMC, PUNE

Special interest- Stroke in Young

Tropical Medicine

High altitude medical problems

Address for communication –

Major (DR) Ashutosh Ojha Colonel (Dr) Sharat Johri

Graded specialist in medicine Senior Advier (Med & Neurology)

170 Military Hospital command Hospital (NC)

PIN-930170 C/O 56 APO

C/O 56 APO

Mobile-09419210649

Note- Due to operational reasons, the exact location of hospitals and other asked for details cannot be provided. Since it is accepted in cases of service doctors, we request you to kindly accept for publication.

170 Military Hospital

C/O 56 APO

May 2007

To

Hon. Editor,Journal of Association of Physicians of India, Turf Estate, #6 & 7, Ground Floor, Opp. Shakti Mills Compound, Dr. E. Moses Road, Opp. Mahalaxmi Station (West), Mumbai 400 011.Tel. : (022) 66663224, 24912218 Tel./Fax : 2492 0263

Sub – submission of article

Sir,

We wish to submit the article “Snakebite – Approach to a case in endemic area” for publication.

Copyright statement

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Further we state to confirm that we have read and approved the contents and also confirm that the manuscript is not submitted or published elsewhere.

We confirm that we have Ethics Committee Approval of our hospital and informed consent from subjects

Colonel (Dr) Sharat Johri Maj (Dr) Ashutosh ojha

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1 International Committee of Medical Journal Editors—Uniform Requirements for Manuscripts Submitted to Biomedical Journals. JAMA 1997; 277: 927-34.

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Maj Ashutosh OjhaGraded specialist (Med) 170 Mil Hosp C/O 56APO (On MOJCC-153,AFMC,Pune) To Commanding officer 170 Mil HospC/O 56 APOSub- request permission for submission of article

Sir ,1. I wish to submit my article titled “Snakebite –Approach to a case in Endemic area” co-authered by senior adviser comprising of our experience in this area for publication to Journal of Association of Physicians of India. Being a common medical emergency encountered in medical practice, our experience will be beneficial to other colleagues managing this emergency medical condition. 2. I further state that the article does contain any classified information and I am not claiming any financial benefit from this publication.3. I request you to kindly grant me your permission to publish this article.

Date May 2007 (Maj Ashutosh Ojha)