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Serum reactions. An analysis of commercial antivenoms and the possible role of anticomplementary activity in de-novo reactions to antivenoms and antitoxins.

Infusion of concentrated heterologous serum proteins may precipitate severe reactions in humans. Some of these reactions are not due to a preexisting hypersensitivity to the foreign protein, but rather to the strongly anticomplementary activity (ACA) of the infused protein. The latter mechanism could account for the occasional anaphylactoid reaction seen in a patient who has had no known previous exposure to the foreign protein. Similarly, it could account for the patient who fails to react to a preliminary subcutaneous trial dose, but then collapses when he is infused later with the same preparation. Nine commercial antivenoms from nine countries were examined and most were found to have high levels of anticomplementary activity. Considerable variation was found in both the immunochemical properties and the anticomplementary activity of these antivenoms. Antitoxins of equine origin to the toxins of diphtheria, tetanus and gas gangrene were also found to have high anticomplementary activity. Because of this activity these preparations should always be diluted and infused slowly. Lack of reaction to a test dose will never guarantee an uneventful infusion, and thus all infusions of heterologous immunoglobulin should be undertaken with the greatest caution and vigilance.

Animals

Antivenomic and Proteomic Assessment of Inter- and Intrapopulation Venom Variations in Nikolsky's Adder Vipera nikolskii: Comparison to Common Adder Vipera berus.

Snake venom variation has important clinical implications, yet individual-level venomics remains limited. We investigated inter- and intrapopulation variability in forest-steppe adder Vipera nikolskii and its recognition by commercial V. berus antivenom using proteomic and immunological approaches. Venoms from 12 individual V. nikolskii specimens representing two geographically distinct populations (BG and KM), together with three pooled V. nikolskii and one pooled V. berus samples were analyzed by LC-MS/MS, ELISA, Western blot, and pull-down assays. Multivariate analysis revealed relative homogeneity in BG and pronounced heterogeneity in KM venoms. Area-based proteomics revealed V. berus venom enrichment in PLA2 (34.6%), SVMP (14.6%), and CRiSP (15.6%), whereas V. nikolskii venoms were more variable. Pooled V. nikolskii venoms showed SVMP abundance (35.2-41.1%), contrasting with lower levels in individual samples. Antivenom binding was stronger for V. berus but weaker and more variable across individual and pooled V. nikolskii samples. Antivenom targeted PLA2/VEGF, CRiSP (only in V. berus), and Kunitz-type proteins. In vivo neutralization assay demonstrated strong protection against V. berus but not V. nikolskii venom. These findings reveal substantial compositional and antigenic variability in V. nikolskii venoms, highlight discrepancies between pooled and individual ones, and underscore the need for region-specific and functionally validated antivenom evaluation.

Animals

Effectiveness of Zagreb antivenom against envenoming by the adder, Vipera berus.

Rhesus monkeys injected subcutaneously with 2, 3, or 4 mg Vipera berus venom per kg body-weight all died in shock. With 1 mg/kg the monkey had severe systemic and local effects taking 12 days to resolve. Five monkeys each recieved 4 mg/kg (a triple-lethal dose) and Zagreb antivenom was injected intravenously 1-4 hours after venom injection. The contents of 2 ampoules (10-8 ml) up to 3 hours later saved the monkeys; at 4 hours later the monkey died. But when the antivenom dose was raised to 16-2 ml 4 hours after venom, it saved the monkey. In addition to saving life, the antivenom greatly reduced the local venom effects. It is suggested that the results justify giving Zagreb antivenom to patients with severe adder-bite poisoning; and it should also be considered in adults to minimise morbidity from local effects.

Adult

Antivenom in sea-snake bit poisoning.

Among a series of 101 patients bitten by sea-snakes in Malaya in the years 1957-64, 80% were fishermen. Bathers and divers are occasionally bitten. Before sea-snake antivenom became available the mortality-rate (despite the high toxicity of sea-snake venom) was only 10%; however, of 11 with serious poisoning, 6 died. Subsequently 10 patients with serious poisoning received specific sea-snake antivenom; 2 patients, admitted moribund, temporarily improved but died, and 8 patients recovered dramatically. In serious poisoning the suitable dosage of intravenous sea-snake antivenom is 3000-10,000 units; in mild poisoning 1000-2000 units should suffice.

Adult

[A technique of accelerated immunization of animals producing antivenom serum].

A technique of "fast" immunization, for antivenom serum production, is reported. Comparatively to the common technique, this fast method is characterized by more numerous immunizing injections (15 instead of 8) during the two first cycles of immunisation, higher venom doses and the lack of the rest period taking place between the two first cycles of immunization in the common technique. By this fast technique one may obtain a highly efficient anti-venmous serum within 2 1/2 to 3 months whereas the common technique needs 3 1/2 to 4 months to obtain the same results.

Animals

Eliciting conditioned taste aversion by cobra venom neurotoxin in rats.

An attempt is made to study conditioned taste aversion (CTA) using cobra venom antivenom or lithium chloride as the Unconditioned Stimulus (US). Twenty-four hour water deprived rats were habituated for two consecutive days to drinking tap water in the drinking box for 15 minutes daily. On 3rd day they were allowed to drink 0.1% sodium saccharin. Thirty minutes later, they were injected with cobra venom (45 micrograms), antivenom (0.022 microliter), antivenom followed by venom, lithium chloride (0.15 M, 4% body weight) or physiological saline. After two days of recovery the animals were water deprived for twenty four hours and water intake was measured on the 7th and 8th day. Retention test on the 9th day shows reduced saccharin consumption in the lithium chloride and venom groups. CTA was significantly reduced in the antivenom-venom group and absent in the antivenom and control group. It is concluded cobra venom can induce clear-cut CTA in rats.

Animals

Bites by foreign venomous snakes in Britain.

In 1970-7 17 people in Britain were the victims of 32 bites by foreign venomous snakes. Crotalus atrox caused eight of these bites, Bitis arietans five, and the remaining 19 bites were caused by 12 different species. All the victims were bitten while handling the snake, and 24 bites were incurred by private individuals in their own homes. Poisoning was negligible in 17 of the 32 bites but life-threatening in at least two cases. Thus in the early stages snake bite may be unpredictable as a clinical problem. All victims of snake bite should be observed for at least 12 hours to assess the severity of poisoning and to ensure rational treatment. Local necrosis developed in six cases and resulted in prolonged illness in five of these cases; local incision was carried out and many have been a casual factor. Comprehensive stocks of antivenoms for treating bites by foreign venomous snakes are held by the National Health Services in Liverpool and London. Antivenom is indicated (a) for potentially serious systemic poisoning, as evidenced by hypotension, electrocardiographic changes, neurtrophilia, and acidosis (after viper or elapid bites), abnormal bleeding or non-clotting blood after viper bites; and ptosis or glossopharyngeal palsy after elapid bites; and (b) for bites from snakes whose venom causes local necrosis, to prevent or minimise this unpleasant complication. For effective antivenom treatment intravenous infusion is mandatory.

Adolescent

Severe conditioned taste aversion elicited by venom of Russell's viper.

Conditioned taste aversion (CTA) established in rats by associating saccharin drinking with subsequent poisoning by Russell's viper venom. Retention test revealed 76 and 56% reduction of saccharin intake in venom and antivenom-venom groups. No CTA was observed in antivenom and control groups.

Animals

Bites by the carpet viper in the Niger Valley.

60 people who had been bitten by the carpet viper, Echis carinatus, were seen in four months at Zungeru Health Centre, in North West Nigeria, where snake-bite patients have recently occupied 10% of beds. Health statistics greatly underestimate the frequency, morbidity, and mortality of snake bite in the rural tropics and further studies will probably confirm other areas endemic for E. carinatus within its vast distribution zone. Regular supplies of effective antivenom are crucial to gain a community's confidence in conventional, as opposed to traditional, treatment. Paramedical staff in a rural clinic can be trained in the definitive management and treatment, including successful antivenom therapy, of most snake-bite patients.

Humans

Adder bites in children.

16 children with adder bites were admitted to hospital in Southampton in the years 1969--77. Two children were severely poisoned; these 2, and a 3rd, fulfilled suggested criteria for antivenom administration but they recovered without it. Three children had no treatment, and 9 children no analgesia. Prolonged morbidity was not seen in these children. Careful observation in hospital was the most important factor in management, with early clinical improvement obviating the need for antivenom.

Adolescent

Proteomic characterization of Tityus championi venom and recombinant expression of its major neurotoxin.

BACKGROUND: Tityus championi is a species endemic to the southern Talamanca Mountain Range, along the border region between Costa Rica and Panama, and has been associated with severe clinical cases. Despite its medical relevance, the composition of its venom remains poorly studied. The present study aimed to characterize the proteomic composition of T. championi venom, identify its main toxin families, and recombinantly produce one of its most abundant and lethal toxins for potential use in antivenom development. METHODS: Venom composition was analyzed by tandem mass spectrometry (MS/MS), enabling the identification of venom proteins. Subsequently, one of its primary lethal toxins (Tcham27) was identified and recombinantly expressed. RESULTS: Proteomic analysis revealed that the most abundant family in the venom corresponded to metalloproteases, with 43 protein groups (17% of the total identifications), which are associated with processes such as hemorrhage, edema, inflammation, hypotension, and necrosis. CIIMET family toxins comprised 27 protein groups (11%). Among ion channel-acting toxins, 18 protein groups (7%) corresponded to sodium channel toxins and 14 (6%) to potassium channel toxins, homologous to components from geographically proximate species such as Tityus discrepans, Tityus cf. asthenes, and Tityus jaimei. Other relevant families included cysteine-rich secretory proteins (CRISPs; 6 proteins, 3%), serine proteases (5 proteins, 2%), and lectins (5 proteins, 2%). In addition, low-abundance components such as insulin-like growth factors, nucleotide pyrophosphatases, hyaluronidase, α-amylase, lipolysis-activated toxins, and chitinase were detected, contributing to the functional diversity of the venom. CONCLUSIONS: Proteomic characterization of T. championi venom demonstrates that metalloproteases constitute a major protein family alongside neurotoxins. Recombinant production of its most abundant toxic peptide, which is identical to toxins in the venom of geographically proximate Tityus species, provides a key tool for developing specific antivenoms.

Protein

Australia's potentially most venomous snake: Parademansia microlepidotus.

Studies on the venom of the small-scaled or fierce snake, Parademansia microlepidotus, suggested that its combination of high toxicity and relatively large venom yield make it the most venomous snake in Australia. The species is distinct from the taipan, but its venom is neutralized by taipan antivenom but not other monospecific antivenoms.

Antivenins