Neutralization of Bothrops alternatus regional venom pools and individual venoms by antivenom: A systematic comparison

Roodt, Adolfo Rafael de; Lanari, Laura Cecilia; Oliveira, Vanessa Costa de; Laskowicz, Rodrigo Daniel; Stock, Roberto P.

doi:10.1016/j.toxicon.2011.04.013

Cited by 18 publications

(7 citation statements)

References 15 publications

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“…The composition of venom and associated toxicity is also theorized to vary across geographical regions [92, 93], as the availability of prey is dependent on the biotic and abiotic factors of the region. Toxicity profiles of N .…”

Section: Discussionmentioning

confidence: 99%

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Beyond the ‘big four’: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies

et al. 2019

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BackgroundSnakebite in India causes the highest annual rates of death (46,000) and disability (140,000) than any other country. Antivenom is the mainstay treatment of snakebite, whose manufacturing protocols, in essence, have remained unchanged for over a century. In India, a polyvalent antivenom is produced for the treatment of envenomations from the so called ‘big four’ snakes: the spectacled cobra (Naja naja), common krait (Bungarus caeruleus), Russell’s viper (Daboia russelii), and saw-scaled viper (Echis carinatus). In addition to the ‘big four’, India is abode to many other species of venomous snakes that have the potential to inflict severe clinical or, even, lethal envenomations in their human bite victims. Unfortunately, specific antivenoms are not produced against these species and, instead, the ‘big four’ antivenom is routinely used for the treatment.MethodsWe characterized the venom compositions, biochemical and pharmacological activities and toxicity profiles (mouse model) of the major neglected yet medically important Indian snakes (E. c. sochureki, B. sindanus, B. fasciatus, and two populations of N. kaouthia) and their closest ‘big four’ congeners. By performing WHO recommended in vitro and in vivo preclinical assays, we evaluated the efficiencies of the commercially marketed Indian antivenoms in recognizing venoms and neutralizing envenomations by these neglected species.FindingsAs a consequence of dissimilar ecologies and diet, the medically important snakes investigated exhibited dramatic inter- and intraspecific differences in their venom profiles. Currently marketed antivenoms were found to exhibit poor dose efficacy and venom recognition potential against the ‘neglected many’. Premium Serums antivenom failed to neutralise bites from many of the neglected species and one of the ‘big four’ snakes (North Indian population of B. caeruleus).ConclusionsThis study unravels disturbing deficiencies in dose efficacy and neutralisation capabilities of the currently marketed Indian antivenoms, and emphasises the pressing need to develop region-specific snakebite therapy for the ‘neglected many’.

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Section: Discussionmentioning

confidence: 99%

“…caeruleus . In addition to geographic variability in venoms [92, 93], the lack of adherence of Indian antivenom manufacturers to international production standards may also result in these undesirable outcomes.…”

Section: Discussionmentioning

confidence: 99%

Beyond the ‘big four’: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies

et al. 2019

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“…For this, it is clear that further work needs to be done to elucidate more medically relevant toxins. Correspondingly, it is important for future research to consider variation in venoms composition to understand how this variability could also influence both envenomation signs and antivenom efficacy 47,48 . The rational concept of using a recombinant neurotoxin with “universal” consensus sequence to produce a broad-specificity anti-elapid antivenom provides the framework for a strategy to develop either animal-derived or recombinant antivenoms.…”

Section: Discussionmentioning

confidence: 99%

Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species

et al. 2019

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Antivenoms are fundamental in the therapy for snakebites. In elapid venoms, there are toxins, e.g. short-chain α-neurotoxins, which are quite abundant, highly toxic, and consequently play a major role in envenomation processes. The core problem is that such α-neurotoxins are weakly immunogenic, and many current elapid antivenoms show low reactivity towards them. We have previously developed a recombinant consensus short-chain α-neurotoxin (ScNtx) based on sequences from the most lethal elapid venoms from America, Africa, Asia, and Oceania. Here we report that an antivenom generated by immunizing horses with ScNtx can successfully neutralize the lethality of pure recombinant and native short-chain α-neurotoxins, as well as whole neurotoxic elapid venoms from diverse genera such as Micrurus , Dendroaspis , Naja , Walterinnesia , Ophiophagus and Hydrophis . These results provide a proof-of-principle for using recombinant proteins with rationally designed consensus sequences as universal immunogens for developing next-generation antivenoms with higher effectiveness and broader neutralizing capacity.

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“…Indian antivenoms are also marketed closer to home, in nearby Pakistan, but studies have shown poor performance against Bungarus and Naja in Pakistan [ 244 ]. Examples of variable cross-reactivity between subspecies of venomous snake include Crotalus scutulatus [ 245 ] and between congeneric species including Micrurus [ 246 , 247 ] and Bothrops [ 248 , 249 , 250 , 251 , 252 , 253 ]. Some medically important genera remain without any effective antivenom including colubrids such as Thelotornis [ 254 ] and lamprophiids such as Atractaspis [ 255 ].…”

Section: Issues and Controversies In Modern Medical Carementioning

confidence: 99%

Snakebite: When the Human Touch Becomes a Bad Touch

Fry

2018

Toxins

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Many issues and complications in treating snakebite are a result of poor human social, economic and clinical intervention and management. As such, there is scope for significant improvements for reducing incidence and increasing patient outcomes. Snakes do not target humans as prey, but as our dwellings and farms expand ever farther and climate change increases snake activity periods, accidental encounters with snakes seeking water and prey increase drastically. Despite its long history, the snakebite crisis is neglected, ignored, underestimated and fundamentally misunderstood. Tens of thousands of lives are lost to snakebites each year and hundreds of thousands of people will survive with some form of permanent damage and reduced work capacity. These numbers are well recognized as being gross underestimations due to poor to non-existent record keeping in some of the most affected areas. These underestimations complicate achieving the proper recognition of snakebite’s socioeconomic impact and thus securing foreign aid to help alleviate this global crisis. Antivenoms are expensive and hospitals are few and far between, leaving people to seek help from traditional healers or use other forms of ineffective treatment. In some cases, cheaper, inappropriately manufactured antivenom from other regions is used despite no evidence for their efficacy, with often robust data demonstrating they are woefully ineffective in neutralizing many venoms for which they are marketed for. Inappropriate first-aid and treatments include cutting the wound, tourniquets, electrical shock, immersion in ice water, and use of ineffective herbal remedies by traditional healers. Even in the developed world, there are fundamental controversies including fasciotomy, pressure bandages, antivenom dosage, premedication such as adrenalin, and lack of antivenom for exotic snakebites in the pet trade. This review explores the myriad of human-origin factors that influence the trajectory of global snakebite causes and treatment failures and illustrate that snakebite is as much a sociological and economic problem as it is a medical one. Reducing the incidence and frequency of such controllable factors are therefore realistic targets to help alleviate the global snakebite burden as incremental improvements across several areas will have a strong cumulative effect.

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Neutralization of Bothrops alternatus regional venom pools and individual venoms by antivenom: A systematic comparison

Cited by 18 publications

References 15 publications

Beyond the ‘big four’: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies

Beyond the ‘big four’: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies

Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species

Snakebite: When the Human Touch Becomes a Bad Touch

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