Causes and Consequences of Snake Venom Variation Casewell, Nicholas R.; Jackson, Timothy N.W.; Laustsen, Andreas H. ...
Trends in pharmacological sciences (Regular ed.),
08/2020, Letnik:
41, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Snake venoms are mixtures of toxins that vary extensively between and within snake species. This variability has serious consequences for the management of the world’s 1.8 million annual snakebite ...victims. Advances in ‘omic’ technologies have empowered toxinologists to comprehensively characterize snake venom compositions, unravel the molecular mechanisms that underpin venom variation, and elucidate the ensuing functional consequences. In this review, we describe how such mechanistic processes have resulted in suites of toxin isoforms that cause diverse pathologies in human snakebite victims and we detail how variation in venom composition can result in treatment failure. Finally, we outline current therapeutic approaches designed to circumvent venom variation and deliver next-generation treatments for the world’s most lethal neglected tropical disease.
Venom is an ecologically important functional trait in venomous snakes and its composition and activity often coevolve with the physiology of the prey animals it is deployed against.Variation in toxin venom components occurs both inter- and intraspecifically as the result of various processes, including gene duplication and the action of positive selection.The consequences of this variation is the generation of functionally diverse venoms that cause distinct pathologies in snakebite victims and which undermine the efficacy of antivenom treatments.Knowledge of the varying toxins found across medically important venoms is enabling the generation of new therapeutic approaches to circumvent venom variation to better treat the worlds 1.8 million annual snakebite victims.
Background: Data on the cost of snakebite injuries may inform key pillars of universal health coverage including proper planning, allocation, and utility of resources. This study evaluated the ...injuries, management, and costs resulting from snakebites at Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH) in Kenya.
Methods: In total, medical records of 127 snakebite victims attending JOOTRH between January 2011 and December 2016 were purposely selected and data on the age, gender, type of residence (urban or rural), part of the body bitten, time of bite, injuries, pre-hospital first aid, time to hospital, length of stay, treatment, and costs were collected. Regression analysis was used to predict the total indirect cost of snakebite injuries and
p≤ 0.05 was considered significant. Mortality and loss of income of hospitalized victims were considered as direct costs.
Results: It was found that 43 victims were 13-24 years of age, 64 were female, 94 were from rural areas, 92 were bitten on the lower limbs, 49 were bitten between 6.00 pm and midnight, 43 attempted pre-hospital first aid, and the median time to hospital was 4.5 hours. Antivenom, supportive therapy, antibiotics, antihistamines, corticosteroids, analgesics, and non-steroidal anti-inflammatory drugs were used. Cellulitis, compartment syndrome, gangrenous foot, psychiatric disorder, and death were the main complications. Most victims spent 1-5 days in hospital and the median cost of treating a snakebite was 2652 KES (~$26). Drugs, ward charges, and nursing procedures were the highest contributors to the total indirect cost. Victims hospitalized for 6-10 days and >10 days incurred 32% and 62% more costs, respectively, compared to those hospitalized for 1-5 days.
Conclusions: The longer snakebite victims are hospitalized, the higher the cost incurred. Continuous medical education on the correct management of snakebites should be encouraged to minimize complications that may increase hospital stays and costs incurred.
Cancer is a global health concern and is still the leading cause of death worldwide, with 10 million deaths caused, so far, by the disease in 2020. Although there are treatments to treat some cancers ...and save lives, these treatments do have drawbacks and can cause side effects. Although various anticancer remedies have been discovered using natural products in the past, none of them went into clinical trials. Scientists still looking for alternative agents, within animal products. Recently venom is gaining attention for its anticancer activities. Objective: The present study, therefore, aimed to address the theoretical possibility that people bitten by venomous snakes may also develop prophylaxis, i.e., natural immunity, against cancer. And whether snake venom can be used as a vaccine due to their similarities with potential cancer antigens or not. Method: An immunoinformatic analysis was performed by correlating potential snake venom components’ amino sequence data with different cancer antigens. Results: Initially, our findings showed that while developed countries have low snakebite rates, they also demonstrated high cancer rates, in contrast to that developing countries, where they have high snakebite rates but low cancer rates. In terms of the immunoinformatic approach, ten cancer antigens have various similarities with five snake venom components. While the amino acid sequence alignment demonstrates similarities below 40%, the antigenicity index scores were found to be high. We predict that an immune system activated in snakebite victims may elicit an immune response against similar epitopes expressed on cancer cells. Hence, victims of snake bites may gain natural immunity against cancer. Conclusion: This study reports that non-lethal snakebites may play a vital role in protecting individuals from developing cancer in the future. Although it is a pilot study, such a concept and findings will open doors for future work to address this finding.
The North African mountain viper (Vipera monticola) is a medically relevant venomous snake distributed in Morocco, Algeria, and Tunisia. Three subspecies of V. monticola, exhibiting differences in ...morphotypes and dietary regimes, are currently recognised: V. m. monticola, V. m. atlantica, and V. m. saintgironsi. Through the application of snake venomics, we analysed the venoms of specimens of Moroccan origin belonging to each of the three subspecies. Snake venom metalloproteinase (svMP), snake venom serine protease (svSP), C-type lectin and C-type lectin-related proteins (CTL), and phospholipase A2 (PLA2) were predominant, with PLA2 being the most abundant toxin family overall. Disintegrins (DI) and cysteine-rich secretory proteins (CRISP) were exclusive to V. m. monticola and V. m. atlantica, while l-amino-acid oxidases (LAAO) were only found in V. m. saintgironsi. The differences detected in the venom profiles, as well as in presence/absence and relative abundances of toxin families, indicate the occurrence of intraspecific venom variation within V. monticola. The identified patterns of venom similarity between subspecies seem to align more with their phylogenetic relationships than with the reported differences in their feeding habits.The North African mountain viper (Vipera monticola) is a medically relevant venomous snake distributed in Morocco, Algeria, and Tunisia. Three subspecies of V. monticola, exhibiting differences in morphotypes and dietary regimes, are currently recognised: V. m. monticola, V. m. atlantica, and V. m. saintgironsi. Through the application of snake venomics, we analysed the venoms of specimens of Moroccan origin belonging to each of the three subspecies. Snake venom metalloproteinase (svMP), snake venom serine protease (svSP), C-type lectin and C-type lectin-related proteins (CTL), and phospholipase A2 (PLA2) were predominant, with PLA2 being the most abundant toxin family overall. Disintegrins (DI) and cysteine-rich secretory proteins (CRISP) were exclusive to V. m. monticola and V. m. atlantica, while l-amino-acid oxidases (LAAO) were only found in V. m. saintgironsi. The differences detected in the venom profiles, as well as in presence/absence and relative abundances of toxin families, indicate the occurrence of intraspecific venom variation within V. monticola. The identified patterns of venom similarity between subspecies seem to align more with their phylogenetic relationships than with the reported differences in their feeding habits.
We aimed to assess the unresolved health issues experienced by a cohort of snakebite survivors and their health-seeking behaviours during the first three months after the snakebite. Patients from the ...Anuradhapura snakebite cohort admitted to the Teaching Hospital Anuradhapura, Sri Lanka, from July 2021 to June 2022 were recruited. Patients were interviewed over the telephone three weeks and three months post-bite to collect data on unresolved health problems post-discharge, patient's adherence to the review plan, newly experienced health issues, health-seeking behaviours and the effect on daily routine. Only snakebite survivors who could be contacted at both three weeks and three months were included. Of 710 eligible patients, 384 (54%) were contactable at both reviews. On discharge from the hospital, 248/384 (65%) had unresolved effects of the snakebite, including 224/384 (58%) who had local effects. The unresolved health problems were reported by patients bitten by H. hypnale (54%), D. russelii (23%), and unidentified snakes (19%). At three weeks and three months, 98/384 (26%) and 52/384 (14%) still had unresolved local effects of envenoming, respectively. Of 144/384 (38%) who were advised to attend review visits post-discharge, mostly to assess renal function, 118 (82%) complied. 112/384 (29%) patients reported self-motivated treatment seeking for unresolved effects of snakebite over the three months. Of them, 87 (78%) visited Sri Lankan indigenous medical practitioners. Patients missed a median of two working days (IQR: 2–4 days) post-discharge. 26 (6.7%) were unable to return to work at 3 weeks, and five patients at 3 months. In rural Sri Lanka, a significant number of viper bite patients leave hospital with mild persistent local effects, which commonly leads to them seeking further treatment. Despite that, almost all snakebite survivors had returned to work at three months post-bite.
Display omitted
•Health-seeking behaviours after hospital discharge is rarely reported.•We followed up 384 snakebite patients after hospital discharge in rural Sri Lanka.•58% of snakebite patients have unresolved health effects when leaving the hospital.•The patients seek treatment for these effects from both indigenous and allopathic practitioners.•Arranging adequate pain relief, wound care and physiotherapy after hospital discharge is important.
For more than a century, concerns about the medical significance of Montpellier snakes, Malpolon spp. (Psammophiidae, Psammophiinae) have been expressed by herpetologists and toxinologists. Although ...some of the opinions have suggested that the most familiar species, the Western Montpellier snake, Malpolon monspessulanus, poses a significant medical risk, only a few detailed, formally documented reports have been published that describe effects in humans. Two reports support a rare risk of systemic envenoming (cranial nerve palsies) after prolonged bites by M. monspessulanus. Relevantly, there has been only one previous report describing a bite by the Eastern Montpellier snake, Malpolon insignitus. Reported here are the effects of a bite inflicted by a 1.1-meter female Malpolon insignitus fuscus in Alborz Province, Iran. The 40-yr-old male victim was handling the snake while preparing to photograph it when he was bitten on the right wrist. The snake remained attached for approximately 40-seconds during which it repeatedly advanced its jaws. The bite caused moderate local envenoming that featured moderate but reportedly notably uncomfortable sharp pain, moderate edema, erythema and pruritis; wound site bleeding was transient and proportional. Full resolution required 5-days; there were no sequelae. The clinical evolution included signs/symptoms consistent with Type I hypersensitivity and subtype Type IV hypersensitivity. Detailed reports of medically significant bites by Malpolon spp. are briefly reviewed and the evidence for medical significance of the genus is evaluated. Management of envenoming by Malpolon spp. is supportive only; almost all victims with qualified medical review have developed only local envenoming that is often mild-moderate. Notably rare systemic effects, e.g., neurotoxicity so far limited to non-progressive cranial nerve palsies, should prompt airway protection, ICU admission, and consultation as indicated. Future study of Malpolon venoms and formal documentation of their bites should increase the evidence quality for the medical risk profile of the genus.
Display omitted
•Local envenoming by Malpolon insignitus fuscus is described•Envenoming featured progressive edema, erythema, pruritis, moderate pain•No systemic effects aside from probable non-specific retro-orbital headache•Full resolution required 5 days•Review/assessment of documented Malpolon spp. envenoming
ABSTRACT
Snakebite envenoming is an important public health issue in many tropical and subtropical countries, where the burden of morbidity and mortality falls particularly on impoverished rural ...communities. Children are an especially vulnerable group. This scoping review provides an overview of the extent, type and content of peer-reviewed evidence regarding factors associated with mortality in snakebite-envenomed children. A comprehensive literature search of MEDLINE and the Global Index Medicus yielded 623 articles, of which 15 met the criteria for inclusion; 67% of studies were conducted in India, with the remaining studies taking place in Papua New Guinea, Morocco and The Gambia. There was a notable scarcity of eligible studies from sub-Saharan Africa and Latin America despite the high burden of envenoming in these regions. The risk factors for mortality that were identified by the greatest number of studies were younger patient age (n=4), delay in administration of antivenom (n=4) and acute kidney injury (n=3). Identification of poor prognostic factors can assist clinicians in making timely referrals to centres with paediatric critical care capability. Future research must address the lack of studies from key geographical regions so that evidence-based improvements to the care of this vulnerable group can be implemented.
Objectives: To assess the risk factors of snake envenomation and the associated complications that patients present with, using data from two different emergency departments in Oman. The secondary ...aim was to describe the common characteristics of the presenting patients. Methods: This multicenter retrospective observational study reviewed all cases presenting with symptoms of snakebite to the emergency departments of Sultan Qaboos University Hospital (tertiary) from March 2016 until August 2017 and Rustaq Hospital (secondary) from August 2015 to August 2017. Results: A total of 212 cases met the inclusion criteria. Coagulopathy was observed in 82 (38.7%) patients, while 14 (6.6%) had acute kidney injury (AKI) and 5 (2.4%) had external bleeding. Of the patients who developed AKI, 85.7% (p < 0.001) had encountered the snake in a valley and initially had bleeding from the site of the bite (p < 0.001) and vomiting (p < 0.007). The delay in receiving the anti-snake venom (ASV) increased the risk of AKI (p < 0.016). Of the patients who developed coagulopathy, 47.6% (p < 0.001) had encountered the snake on a farm and 72.0% (p < 0.002) received the bite to a lower limb. Increased time from bite to ASV was associated with development of coagulopathy (p < 0.001). No patient death was recorded. Conclusions: The location (terrain) where the snake was encountered was associated with the patient's risk for either AKI or coagulopathy, which suggests the preference of different snake species to different types of habitat. The time elapsed between the bite and the ASV administration was associated with higher risk of development of AKI or coagulopathy.
PDF
