PHYSIOLOGICAL MANIFESTATIONS UNDER VENOM INTERACTION AND THEIR ANALYSIS

Abstract

Venom is a survival tool for some non-chordate and chordate creature. Venom plays important roles in defense, hunting and ex-vivo digestion. Although, venom is meant to control and digest small insects, amphibians, rodents and reptiles, the venom interaction may result disturbances in the circulatory, neuronal and lymphatic systems of the human body as well. The different constituents present in the venom cause decomposition of cells, tissues and organisms in the body of the victim. Their isolated and synergistic actions result very adversely on the human and animal body systems, when they enter into the biological systems. India, being a tropical country, inhabits number of snake and scorpion species. Chief venomous snakes in India are cobra (Naja Naja) and common krait (Bungarus Caeruleus) belonging to Elapidae; while Russell's viper (Daboia Russelli) and Sawscaled viper (Echis Carinatus) belong to Viperidae families. Other venomous species of snakes like king cobra (Ophiophagus Hannah), banded krait (Bungarus Fasciatus) and colubrids have less aggression towards human beings and the cases of snake bites of these species are considered medically insignificant in India. In Arachnids (invertebrate phylum arthropoda), spiders, giant black scorpion {Palamneus sp.) and the Indian red scorpion (Mesobuthus Tamulus Concanesis) are medically important. A large number of venom interactions take place in India every year and thousands of people die due to bites and stings. Only a small but still significant number ofpatients get admitted to the hospitals, mostly in terminal state with varied symptoms and doubtful history before the attending medical staff. So, it is highly probable that a patient is bitten by one snake species and he is administered Anti Snake Venom (ASV) intended for another species. Even non-venomous bites may be administered ASV and venomous bites are not treated with ASV. In such situations, the patient would suffer unreasonably. To reduce the risks of misclassification, only polyvalent ASV is being made, marketed and prescribed in India; which is many times costlier than equally potent mono-specific ASV. Even with the polyvalent ASV, the problem of misclassification remains, if the aggressor species is a scorpion, whose venom may also result in neurotoxic symptoms, enough to confuse at a first glance for anelapid snake envenomation or vice-versa. A large number of case reports of the envenomation can be observed with varied degrees of experiences in medical management. A number of epidemiological studies were also published but with little stress on the identification of the aggressor species. Thus, a need was felt for a combinational and comparative study regarding the envenomation by different species. To identify the aggressor species, different methods have been devised and tried in the past but with limited success. A number of field experts from medical practices and the WHO have felt the need for a reliable method of species identification, which can be used in the critical conditions. The work being presented here is an attempt to study physiological manifestations due to the accidental venom interactions in human beings. Because of the species specific variations in physiological parameters, a careful examination of symptoms and other parameters, species can be identified and quantity of venom injectedcan be estimated. A number of patient records and publications were referred and the symptoms due to venom interaction were studied. Correlating with the species, sets of species specific symptoms were identified. It was also considered that the symptoms should be either visual or should require minimal instrumentation. Based on these symptoms, a patient data form was designed. The form contained fields for symptoms and also some useful statistical information about the patient and the aggressor species. The statistical data was acquired from the patient or attendant (if the patient was not in a state to explain) andthe symptom datawas provided by the attending medical staff. Adhering to the ethical guidelines, issued by a competent authority for the current study, the patient/attendants were explained the purpose of the datacollection and their written permission was obtained for academic use of the information. Out of 97 admitted patients, 39 patients qualified for participation in the study. The qualifying patients comprised of venom interaction cases of all the four medically important snakes, Indian red scorpion and recluse spider and were designated in six con-specific envenomation classes. One non-venomous bite was also included as a true negative case. As per the patient data form, 32 parameters and symptoms were obtained from the patients. It was mandatory that for at least one species, each symptom value should be complimentary to the rest of the species. 29 symptoms and parameters qualified in this criterion. Normalized values of three statistical parameters, viz. age, delay in transportation and Sp02 were also used in the analysis. xviii The analysis of the data revealed that the development of certain symptoms due to envenomation by a particular species depends upon the severity of envenomation as well as the physical status of the victim and the delay in medical assistance. This study led to the development of a two dimensional table of species and severity specific symptoms. This method does not require any instrumentation and can be used heuristically. A decision tree classification method was also developed with top-down observations, terminating in a classification at the bottom of the decision tree. In this method, the vital life signs are first identified and when the patient is stabilized, the visual and minimal instrumentation symptoms form branches ofthe decision tree. Pupillary reaction to light may provide vital clues in classifying the envenomation either due to elapid snakes, scorpion sting or due to viperine bites. Further decisive symptoms may branch for species specific classification. However, to make the classifier exhaustive, the classifier contains two more classes, non-venomous interaction and other physiological conditions. This method is simpler butdoes not contain severity grade classification. Because of a large number of symptoms and parameters having non-exclusive and overlapping nature over the species classes, the analysis of the symptomatology was fairly complex. Some symptoms and parameters manifested in more than one classes did not manifest in mild envenomation cases and some symptoms were common in more than one class. Hence, the analysis resulted in development ofa perceptron type neural network, incorporating symptoms and other statistical details as input and the species and degree of severity as output. The neural network was field tested. There was no error identified in species identification and insignificant error was observed in severity estimation. The cardiovascular system is the most susceptible system in the human body and variation in any other body system is reflected in the cardiovascular system. The electrocardiogram (ECG) represents the cardiac events and also macroscopic representation of the myocardial musculature health. The quantitative analysis of the ECG signal from the patients revealed significant changes under venom interaction. Repeated ECG during the course oftreatment did show the return to normal tendency in a number of abnormal parameters, indicating improvement. A number of species specific parameter changes were observed in the ECG signal and a few symptoms exhibited some marked morphological changes xix pertaining to specific species. Thus the ECG signal can also yield vital information for species identification and severity of envenomation. P wave identification in ECG has been a challenge due to its morphology, susceptibility to noise and inconsistent onset and offset across the leads. Three methods of P wave identification were also developed to improve the efficiency of the software analysis. It was observed that all the species venom contain constituents that affect the cardiac activities. It was found that the right pre-cordial leads are the most susceptible to venom interaction. The QTc intervals were found prolonged in all types of venoms. There were some species specific features identified in electrocardiograms. The cobra bite cases indicated ST-T level changes patterns similar to myocardial ischemia. The krait bite cases manifested clear U waves which are often not seen in regular electrocardiograms. Uwaves, alongwith the QTc prolongation and ST depression might be indicative of hypokalemia. It was also observed that the hyperkalemia in scorpion sting cases had poor correlation to ECG changes. Due to some similarities in physiological manifestations between scorpion stings and krait bites, there exist possibilities ofmisclassification. Evidences from other symptoms and electrocardiograms may be useful in ruling out the misclassification. It can be stated that this work may prove to be helpful in species classification and envenomation grade identification. The species identification may be useful in anticipating the subsequent symptomatic emergencies and prescription of mono-specific ASV. The severity grade identification is useful inestimation and scheduling of the ASV dose for the patient. If applied, this work may help in paving way for a balanced mono specific ASV administration as compared to the prevailing overdosed costly polyvalent ASV administration. XX