Reminiscences from indian pediatrics: a tale
of 50 years |
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Indian Pediatr 2019;56:
323-324 |
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Scorpion Envenomation to Therapeutics
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Aashima Dabas
Department of Pediatrics, Maulana Azad Medical College, New Delhi,
India.
EMAIL:
[email protected]
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T he March 1969 issue of Indian Pediatrics
included interesting research papers on scorpion envenomation, mass
measles vaccination, intellectual disability (then mental retardation),
poisoning, septic meningitis, and tubercular meningitis. We selected the
study of physiological effects of scorpion envenomation for the present
review as it is a common medical emergency in coastal and rural areas of
India with case fatality being higher in children than adults. The study
presents landmark research in establishing cardiac and behavioral
changes after scorpion envenomation, which now form the basis of its
treatment strategy.
The Past
The study [1] was an animal experiment conducted
in Andhra Pradesh, which was house to two types of poisonous scorpions
(small, red Buthustamulus and large, black
Palamneus-gravimonus). The scorpion venom was initially thought to
be only neurotoxic as it was associated with severe local pain followed
by brainstem involvement and death. The authors aimed to establish the
cardiovascular effects of the poison as signs of myocarditis were
observed in children who succumbed to scorpion sting. The authors
experimentally extracted the poison from scorpions and injected it
intravenously in fifteen anesthetized dogs and three rabbits, and
intraperitoneally in three rats in varying concentrations. Two dogs
succumbed after high-dose poison (>200 µg) administration with fatal ECG
changes within two and half hours. The surviving dogs showed initial
rise in blood pressure (by 50-60 mmHg by 5th minute) followed by a
gradual decline that was associated with respiratory depression. Sinus
tachycardia was seen in clinically asymptomatic dogs after 48-72 hours
who had received less dose (35-100 µg) of poison. Higher dose of poison
was associated with sinus tachycardia followed by sinus bradycardia, and
later with ventricular extrasystoles and changes of toxic myocarditis.
The rabbits and rats developed marked prostration, dilatation of pupils,
salivation and urination. A dose-dependent response was established.
Historical background and past knowledge:
Scorpions are known to be one of the deadliest and poisonous species on
Earth, mentioned even in ancient Indian vedas – Rig Veda and Atharva
Veda. Scorpions have also been mentioned in the history of Middle-East,
Indus valley civilization and Egyptian civilization. The deadly, fetish
and vengeful attributes of the arthropod were notable in early ancient
Egypt where rulers were known as ‘Scorpion King’ – later also filmed as
movie series. Idols of scorpion goddesses are worshipped in eastern and
southern parts of India.
Scorpions thrive well in dry climates globally and
are classified as old and new world scorpion belonging to Eastern and
Western hemisphere, respectively. There are about 86 species of scorpion
in India out of which the Buthidae family is the most lethal. One
of the earliest case report of scorpion bite from India dates back to
1926, manifesting as generalized pain, shock and pulmonary edema [2].
This case received local wound care and a concoction of whisky,
intradermal caffeine and atropine along with supportive general
measures. Numerous medicinal plants have been used since ancient times
for their anti-inflammatory, anti-pruritic and analgesic properties in
Eastern Asia. There are few reports of immunotherapy being practiced in
ancient times. An ancient researcher from Iran practiced self-injection
of small quantities of scorpion poison to induce tolerance. Scorpions
were placed in sesame oil, which was topically applied to sting site as
an antidote.
The Present
Toxicology has evolved from mere recognition and
management of scorpion bites to better understanding of venom
composition and its chemical use. The scorpion venom has been
extensively studied for its varied chemical properties. The composition
of scorpion toxin is water, salts, lipids, proteins, nucleotides,
biogenic amines, enzymes and peptides. The toxin acts on voltage gated
ion (sodium, potassium and calcium) channels to function as neurotoxin,
cardiotoxin, nephrotoxin, hemolytic toxin and as enzymes [3]. The sodium
channel toxins (alpha toxins) cause prolonged depolarization with
neuronal excitation and are the most deleterious to mammals. The
inactivation of sodium channels results release of catecholamine with an
autonomic storm seen as sweating, salivation, cardiovascular
instability, arrhythmias and increased respiratory secretions [4]. Death
usually occurs from pulmonary edema, myocardial injury or lethal
arrhythmias as was shown in the reviewed study [1]. The potassium
channel toxins play role in T-cell mediated autoimmune diseases.
Approximately 1,50,000 polypeptides in venoms from different scorpion
species have been discovered. Scorpion venom has now been exploited for
medicinal use as antibacterial, antifungal, anticancer agent, and
against multi-drug resistant microorganisms or superbugs [3]. The
immunological role of similar peptides contained in venom extracts is
evolving with continued research.
The lethality of venom is dependent upon scorpion
species, dose (as was also concluded in present study) and host response
to sting. The main treatment approach in scorpion sting includes pain
relief and first aid, cardiovascular support and antivenom
administration. Pain due to local neurotoxicity is usually severe and
its relief has been central to the management of scorpion sting. Various
agents like topical lidocaine, paracetamol infusion and ice compresses
have been used. The use of systemic steroids, antihistaminics or
calcium-channel blockers has not shown any clinical benefit [4].
Cardiotoxicity is a hallmark of scorpion sting as was also reported by
the reviewed paper for the first time from India [1]. Prazosin, a
selective a-1
adrenergic blocker is the pharmacological antidote, and is recommended
for alleviating cardiovascular and autonomic symptoms of scorpion sting.
Use of prazosin is associated with decreased incidence of massive
pulmonary edema which has improved survival in affected children [5].
Scorpion antivenom has been found efficacious for new world scorpion
envenomation but not for old world scorpions that inhabit India. A
recent meta-analysis reported similar rate of clinical recovery between
antivenom and placebo groups [6]. Data on 53 patients from India
reported prazosin to be superior than antivenom in clinical recovery and
survival [7]. A combination therapy of antivenom with prazosin hastened
recovery than use of prazosin alone [8]. Abnormal echocardiography at
admission may predict the need for a second dose of antivenom in Indian
children after scorpion bites [9]. Recent developments in immunotherapy
are underway with use of avian antisera and less toxic adjuvants [10].
References
1. Rao P, BK P, Bhatt V, Harnath PSRK. Cardiac and
behavioural effects of scorpion venom in experimental animals. Indian
Pediatr. 1969;3:95-101.
2. Lang MC. A case of scorpion-bite. Indian Med Gaz.
1926;61:553-4.
3. Ortiz E, Gurrola GB, Schwartz EF, Possani LD.
Scorpion venom components as potential candidates for drug development.
Toxicon. 2015; 93:125-35.
4. Bawaskar HS, Bawaskar PH. Scorpion envenoming – a
step ahead. Indian Pediatr. 2015; 52:289-90.
5. Bawaskar HS, Bawaskar PH. Clinical profile of
severe scorpion envenomation in children at rural setting. Indian
Pediatr. 2003;40:1072-5.
6. Rodrigo C, Gnanathasan A. Management of scorpion
envenoming: a systematic review and meta-analysis of controlled clinical
trials. Syst Rev. 2017;6:74.
7. Bawaskar HS, Bawaskar PH. Utility of scorpion
antivenin vs prazosin in the management of severe Mesobuthustamulus
(Indian red scorpion) envenoming at rural setting. J Assoc Physicians
India. 2007;55:14-21.
8. Kumar PM, Krishnamurthy S, Srinivasaraghavan R, Mahadevan
S, Harichandrakumar KT. Predictors of myocardial dysfunction in children
with Indian red scorpion (Mesobuthustamulus) sting envenomation.
Indian Pediatr. 2015;52:297-301.
9. Abimannane A, Rameshkumar R, Satheesh P, Mahadevan
S. Second dose of scorpion antivenom in children with Indian red
scorpion (Mesobuthustamulus) sting envenomation. Indian Pediatr. 2018;55:315-8.
10. Nouri A, Nait Mohamed FA, Laraba-Djebari F. New
and safe formulation for scorpion immunotherapy: Comparative study
between saponin and FCA adjuvants associated to attenuated venom.
Vaccine. 2018; 36:1720-7.
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