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1.
PLoS One ; 17(5): e0268402, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35594256

RESUMO

A new cryptic species of green pit viper is described from northeast India, based on specimens collected from the state of Mizoram and Meghalaya. The new species is a member of the subgenus Viridovipera and is sister to Trimeresurus medoensis based on molecular data for mitochondrial cytochrome b gene, whereas resembles Trimeresurus gumprechti morphologically. A combination of characters helps delimit the new species from its congeners. Description of the new species highlights the need for dedicated surveys across northeast India to document its reptilian diversity, as this represents the third new species of the genus to be described in the past three years.


Assuntos
Mordeduras de Serpentes , Trimeresurus , Viperidae , Animais , Antivenenos , Índia , Trimeresurus/genética , Viperidae/genética
2.
Dokl Biochem Biophys ; 503(1): 98-103, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35538287

RESUMO

To search for compounds with antiprotozoal activity, effects of snake venoms on the ciliates Tetrahymena pyriformis was studied. T. pyriformis from subkingdom of Protozoa, including the protozoal pathogens, was used as a model organism to select the venoms that are the most active against parasitic protozoans. Various concentrations of venoms were added to the cells, and the cells that survived after 24 h were counted. Among the six snake species from the Viperidae family, the venom of the viper Vipera berus, which completely killed the cells at 49 µg/mL, was the most active. Among four species from the Elapidae family, the previously studied cobra venoms containing cytotoxins with strong antiprotozoal activity as well as the venom of krait Bungarus multicinctus (10 µg/mL) were the most active. The venoms of the pit vipers and Nikolsky's viper did not show any activity at 12.5 mg/mL. Thus, the venoms of V. berus and B. multicinctus are promising for the isolation of new antiprotozoal compounds.


Assuntos
Tetrahymena pyriformis , Viperidae , Animais , Bungarus , Venenos Elapídicos , Elapidae , Venenos de Serpentes , Venenos de Víboras
3.
Zoology (Jena) ; 152: 126013, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35468446

RESUMO

Venomous viperid snakes possess relatively large and fragile hollow fangs that are an integral part of the envenomation apparatus for predation. We hypothesized that fangs serve like disposable needles and predicted a high loss rate and, hence, high replacement rate in free-ranging snakes. Snakes also possess smaller rear teeth that aid in gripping and swallowing the prey. We reasoned that these teeth are less delicate than fangs and predicted that their loss would be at a slower rate than fangs. To test our predictions, we analyzed fecal samples of free-ranging Saharan sand vipers, Cerastes vipera, in the Northern Negev desert, Israel. Close to 25% of fecal samples contained fangs, averaging more than one fang per sample and, consequently, our first prediction was supported. We estimated that fangs are replaced each fourth predation, and that replacement rate under natural conditions is at a high rate of approximately every twenty days. Fecal samples contained rear teeth at the same proportion as fangs, which indicated that the rapid replacement of teeth was not limited only to fangs and, therefore, our second prediction was not supported. These findings reflect the importance of both front fangs and rear teeth in the hunting of prey in free-ranging C. vipera. This is the first quantitative report of fang and rear teeth loss in a free-ranging viperid which is based on their recovery in feces; and we believe that similar high rates of loss occur in other viperid species.


Assuntos
Dente , Viperidae , Animais , Israel , Comportamento Predatório , Dente/anatomia & histologia
4.
Toxins (Basel) ; 14(4)2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35448845

RESUMO

Bitiscetin-1 (aka bitiscetin) and bitiscetin-2 are C-type lectin-like proteins purified from the venom of Bitis arietans (puff adder). They bind to von Willebrand factor (VWF) and-at least bitiscetin-1-induce platelet agglutination via enhancement of VWF binding to platelet glycoprotein Ib (GPIb). Bitiscetin-1 and -2 bind the VWF A1 and A3 domains, respectively. The A3 domain includes the major site of VWF for binding collagen, explaining why bitiscetin-2 blocks VWF-to-collagen binding. In the present study, sequences for a novel bitiscetin protein-bitiscetin-3-were identified in cDNA constructed from the B. arietans venom gland. The deduced amino acid sequences of bitiscetin-3 subunits α and ß share 79 and 80% identity with those of bitiscetin-1, respectively. Expression vectors for bitiscetin-3α and -3ß were co-transfected to 293T cells, producing the heterodimer protein recombinant bitiscetin-3 (rBit-3). Functionally, purified rBit-3 (1) induced platelet agglutination involving VWF and GPIb, (2) did not compete with bitiscetin-1 for binding to VWF, (3) blocked VWF-to-collagen binding, and (4) lost its platelet agglutination inducing ability in the presence of an anti-VWF monoclonal antibody that blocked VWF-to-collagen binding. These combined results suggest that bitiscetin-3 binds to the A3 domain, as does bitiscetin-2. Except for a small N-terminal fragment of a single subunit-which differs from that of both bitiscetin-3 subunits-the sequences of bitiscetin-2 have never been determined. Therefore, by identifying and analyzing bitiscetin-3, the present study is the first to present the full-length α- and ß-subunit sequences and recombinant expression of a bitiscetin-family toxin that blocks the binding of VWF to collagen.


Assuntos
Viperidae , Fator de von Willebrand , Aglutinação , Animais , Sítios de Ligação , Plaquetas/metabolismo , Colágeno/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Peptídeos/farmacologia , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Ligação Proteica , Venenos de Serpentes , Viperidae/metabolismo , Fator de von Willebrand/metabolismo
5.
Int J Biol Macromol ; 206: 990-1002, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35321814

RESUMO

Bothorps atrox is responsible for most of the ophidism cases in Perú. As part of the envenoming, myotoxicity is one of the most recurrent and destructive effects. In this study, a myotoxin, named BaMtx, was purified from B. atrox venom to elucidate its biological, immunological, and molecular characteristics. BaMtx was purified using CM-Sephadex-C-25 ion-exchange resin and SDS-PAGE analysis showed a unique protein band of 13 kDa or 24 kDa under reducing or non-reducing conditions, respectively. cDNA sequence codified a 122-aa mature protein with high homology with other Lys49-PLA2s; modeled structure showed a N-terminal helix, a ß-wing region, and a C-terminal random coil. This protein has a poor phospholipase A2 enzymatic activity. BaMtx has myotoxic (DMM = 12.30 ± 0.95 µg) and edema-forming (DEM = 26.00 ± 1.15 µg) activities. Rabbit immunization with purified enzyme produced anti-BaMtx antibodies that reduced 50.28 ± 10.15% of myotoxic activity and showed significant cross-reactivity against B. brazili and B pictus venoms. On the other hand, BaMtx exhibits mild anti-proliferative and anti-migratory effects on breast cancer cells, affecting the ROS and NADH levels, which may reduce mitochondrial respiration. These results contribute to the understanding of B. atrox Lys49-PLA2 effects and establish the anticancer potential de BaMtx.


Assuntos
Bothrops , Venenos de Crotalídeos , Viperidae , Sequência de Aminoácidos , Animais , Bothrops/metabolismo , Miotoxicidade , Peru , Fosfolipases A2/química , Coelhos , Viperidae/metabolismo
6.
PLoS Negl Trop Dis ; 16(3): e0010292, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35344557

RESUMO

Envenoming by the hump-nosed pit viper (Hypnale hypnale) raises concern as it inflicts significant debilitation and death in the Western Ghats of India and in the adjacent island nation of Sri Lanka. In India, its medical significance was realized only during 2007 due to its misidentification as Echis carinatus and sometimes as Daboia russelii. Of late, several case reports have underlined the ineptness of the existing polyvalent anti-venom therapy against H. hypnale envenoming. Currently, H. hypnale bite has remained dreadful in India due to the lack of neutralizing anti-venom therapy. Hence, this study was undertaken to establish a systematic comparative, biochemical, pathological, and immunological properties of Sri Lankan H. hypnale venom alongside Indian E. carinatus, and D. russelii venoms. All three venoms differed markedly in the extent of biochemical activities including proteolytic, deoxyribonuclease, L-amino acid oxidase, 5'-nucleotidase, hyaluronidase, and indirect hemolytic activities. The venoms also differed markedly in their pathological properties such as edema, hemorrhage, myotoxic, cardiotoxic, and coagulant activities. The venoms showed stark differences in their protein banding pattern. Strikingly, the affinity-purified rabbit monovalent anti-venoms prepared against H. hypnale, E. carinatus, and D. russelii venoms readily reacted and neutralized the biochemical and pathological properties of their respective venoms, but they insignificantly cross-reacted with, and thus failed to show paraspecific neutralization of any of the effects of the other two venoms, demonstrating the large degree of variations between these venoms. Further, the Indian therapeutic polyvalent anti-venoms from VINS Bioproducts, and Bharath Serums and Vaccines failed to protect H. hypnale venom-induced lethal effects in mice.


Assuntos
Crotalinae , Víbora de Russell , Viperidae , Animais , Antivenenos/farmacologia , Antivenenos/uso terapêutico , Humanos , Camundongos , Coelhos , Venenos de Víboras
7.
Adv Protein Chem Struct Biol ; 129: 435-477, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35305724

RESUMO

Snakebite envenoming (SBE) leads to significant morbidity and mortality, resulting in over 90,000 deaths and approximately 400,000 amputations annually. In sub-Saharan Africa (SSA) alone, SBE accounts for over 30,000 deaths per annum. Since 2017, SBE has been classified as a priority Neglected Tropical Disease (NTD) by the World Health Organisation (WHO). The major species responsible for mortality from SBE within SSA are from the Bitis, Dendroaspis, Echis and Naja genera. Pharmacologically active toxins such as metalloproteinases, serine proteinases, 3-finger toxins, kunitz-type toxins, and phospholipase A2s are the primary snake venom components. These toxins induce cytotoxicity, coagulopathy, hemorrhage, and neurotoxicity in envenomed victims. Antivenom is currently the only available venom-specific treatment for SBE and contains purified equine or ovine polyclonal antibodies, collected from donor animals repeatedly immunized with low doses of adjuvanted venom. The resulting plasma or serum contains a high titre of specific antibodies, which can then be collected and stored until required. The purified antibodies are either whole IgG, monovalent fragment antibody (Fab) or divalent fragment antibody F(ab')2. Despite pharmacokinetic and pharmacodynamic differences, all three are effective in the treatment of SBE. No antivenom is without adverse reactions but, the level of their impact and severity varies from benign early adverse reactions to the rarely occurring fatal anaphylactic shock. However, the major side effects are largely reversible with immediate administration of adrenaline and corticosteroids. There are 16 different antivenoms marketed within SSA, but the efficacy and safety profiles are only published for less than 50% of these products.


Assuntos
Mordeduras de Serpentes , Viperidae , África ao Sul do Saara , Animais , Antivenenos/farmacologia , Antivenenos/uso terapêutico , Cavalos , Fatores Imunológicos/uso terapêutico , Imunoterapia , Ovinos , Mordeduras de Serpentes/tratamento farmacológico
8.
Artigo em Inglês | MEDLINE | ID: mdl-35248757

RESUMO

The viperid snake genus Bothriechis consists of eleven species distributed among Central and South America, living across low and high-altitude habitats. Despite Bothriechis envenomations being prominent across the Central and South American region, the functional effects of Bothriechis venoms are poorly understood. Thus, the aim of this study was to investigate the coagulotoxic and neurotoxic activities of Bothriechis venoms to fill this knowledge gap. Coagulotoxic investigations revealed Bothriechis nigroviridis and B. schlegelii to have pseudo-procoagulant venom activity, forming weak clots that rapidly break down, thereby depleting fibrinogen levels and thus contributing to a net anticoagulant state. While one sample of B. lateralis also showed weaker pseudo-procoagulant activity, directly clotting fibrinogen, two samples of B. lateralis venom were anticoagulant through the inhibition of thrombin and factor Xa activity. Differential efficacy of PoliVal-ICP antivenom was also observed, with the pseudo-procoagulant effect of B. nigroviridis venom poorly neutralised, despite this same activity in the venom of B. schlegelii being effectively neutralised. Significant specificity of these fibrinogen cleaving toxins was also observed, with no activity upon model amphibian, avian, lizard or rodent plasma observed. However, upon avian plasma the venom of B. nigroviridis exerted a complete anticoagulant effect, in contrast to the pseudo-procoagulant effect seen on human plasma. Neurotoxic investigations revealed B. schlegelii to be unique among the genus in having potent binding to the orthosteric site of the alpha-1 postsynaptic nicotinic acetylcholine receptor (with B. lateralis having a weaker but still discernible effect). This represents the first identification of postsynaptic nAChR neurotoxic activity for Bothriechis. In conclusion this study identifies notable differential activity within the coagulotoxic and postsynaptic neurotoxic activity of Bothriechis venoms, supporting previous research, and highlights the need for further studies with respect to antivenom efficacy as well as coagulotoxin specificity for Bothriechis venoms.


Assuntos
Venenos de Crotalídeos , Viperidae , Animais , Anticoagulantes/toxicidade , Antivenenos/farmacologia , Venenos de Crotalídeos/toxicidade , Fibrinogênio/metabolismo , Árvores/metabolismo , Viperidae/metabolismo
9.
Mil Med ; 187(5-6): 113-115, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35284928

RESUMO

Medical students at the Uniformed Services University of the Health Sciences participate in a leadership curriculum designed to develop leadership skills. Operation Bushmaster is a 5-day field practicum designed to test these skills. In this article, we describe 10 leadership lessons learned during Operation Bushmaster applicable to all leaders.


Assuntos
Estudantes de Medicina , Viperidae , Animais , Currículo , Humanos , Liderança
10.
Molecules ; 27(5)2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35268832

RESUMO

Snakebite remains a significant public health burden globally, disproportionately affecting low-income and impoverished regions of the world. Recently, researchers have begun to focus on the use of small-molecule inhibitors as potential candidates for the neutralisation of key snake venom toxins and as potential field therapies. Bitis vipers represent some of the most medically important as well as frequently encountered snake species in Africa, with a number of species possessing anticoagulant phospholipase A2 (PLA2) toxins that prevent the prothrombinase complex from inducing clot formation. Additionally, species within the genus are known to exert pseudo-procoagulant activity, whereby kallikrein enzymatic toxins cleave fibrinogen to form a weak fibrin clot that rapidly degrades, thereby depleting fibrinogen levels and contributing to the net anticoagulant state. Utilising well-validated coagulation assays measuring time until clot formation, this study addresses the in vitro efficacy of three small molecule enzyme inhibitors (marimastat, prinomastat and varespladib) in neutralising these aforementioned activities. The PLA2 inhibitor varespladib showed the greatest efficacy for the neutralisation of PLA2-driven anticoagulant venom activity, with the metalloproteinase inhibitors prinomastat and marimastat both showing low and highly variable degrees of cross-neutralisation with PLA2 anticoagulant toxicity. However, none of the inhibitors showed efficacy in neutralising the pseudo-procoagulant venom activity exerted by the venom of B. caudalis. Our results highlight the complex nature of snake venoms, for which single-compound treatments will not be universally effective, but combinations might prove highly effective. Despite the limitations of these inhibitors with regards to in vitro kallikrein enzyme pseudo-procoagulant venom activity, our results further support the growing body of literature indicating the potential use of small molecule inhibitors to enhance first-aid treatment of snakebite envenoming, particularly in cases where hospital and thus antivenom treatment is either unavailable or far away.


Assuntos
Viperidae , Animais
11.
Toxicon ; 211: 44-49, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35317994

RESUMO

Mexico is home to an extreme diversity of herpetofauna, with venomous snakes imposing a significant burden upon public health. However, little is known about the pathophysiological venom actions of a number of potentially medically important species, including those from the genera Mixcoatlus and Ophryacus. Our study aimed to fill this knowledge gap by ascertaining the effects of Mixcoatlus melanurus, Ophryacus smaragdinus and Ophryacus sphenophrys venoms upon the coagulation cascade utilising a series of well-validated coagulation assays. While M. melanurus venom exhibited no significant coagulotoxic activities, both O. smaragdinus and O. sphenophrys venoms exerted multiple coagulotoxic activities upon the coagulation cascade which would be contributing towards a net anticoagulant venom activity. O. sphenophrys significantly inhibited the spontaneous clotting of plasma but O. smaragdinus did not. They differed in that O. sphenophrys inhibited the clotting enzymes factor IXa and factor XIa. However, O. smaragdinus was able to inhibit factor Xa in isolation-assays. Both O. smaragdinus and O. sphenophrys degraded fibrinogen, with O. smaragdinus venom causing a significantly weaker fibrinogen clot than O. sphenophrys. In vitro antivenom efficacy assays were undertaken to ascertain the efficacy of Antivipmyn-Tri antivenom (which is made using Bothrops, Crotalus, and Lachesis venoms). This antivenom was chosen due to the phylogenetic uncertain position of the Ophryacus, but with some molecular genetics' studies placing it as sister to Lachesis. Despite the complexity of the antivenom immunising mixture, the anticoagulant activity of O. sphenophrys venom was relatively poorly neutralised by the antivenom. This work contributes to the understanding of the functional activity of Mixcoatlus and Ophryacus venoms, laying a foundation for future work investigating the coagulotoxins present within Ophryacus venoms in addition to providing data useful for the evidence-based design of clinical management strategies for the envenomed patient.


Assuntos
Crotalinae , Viperidae , Animais , Anticoagulantes/farmacologia , Antivenenos/farmacologia , Humanos , Filogenia
12.
Pan Afr Med J ; 41: 50, 2022.
Artigo em Francês | MEDLINE | ID: mdl-35317478

RESUMO

Snake bite is the most severe type of envenomation. Annual incidence exceeds six million, with high mortality rates. Viper bites are often responsible for coagulopathy, which causes bleeding disorders. However, ischemic complications are rare. We here report the case of a 6-year-old girl victim of a viper [genus Cerastes] bite in the left ankle. She was admitted with disorders of consciousness and disseminated intravascular coagulation 4 days after the bite. Clinical examination showed left hemiparesis and left lower limb viperin syndrome. Brain CT scan objectified right temporoparietal ischemia. The patient outcome was marked by neurological worsening, requiring mechanical ventilation. Stroke, in particular ischemic stroke secondary to severe snake envenomation, is exceptional. The physiopathological mechanism has not been clearly elucidated but it appears to be multifactorial. Then new studies are needed.


Assuntos
Coagulação Intravascular Disseminada , AVC Isquêmico , Mordeduras de Serpentes , Acidente Vascular Cerebral , Viperidae , Animais , Criança , Feminino , Humanos , Mordeduras de Serpentes/complicações , Acidente Vascular Cerebral/complicações
13.
Curr Drug Targets ; 23(2): 126-144, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35139779

RESUMO

The emergence of multi-drug resistant bacteria and limitations on cancer treatment represent two important challenges in modern medicine. Biological compounds have been explored with a particular focus on venoms. Although they can be lethal or cause considerable damage to humans, venom is also a source rich in components with high therapeutic potential. Viperidae family is one of the most emblematic venomous snake families and several studies highlighted the antibacterial and antitumor potential of viper toxins. According to the literature, these activities are mainly associated to five protein families - svLAAO, Disintegrins, PLA2, SVMPs and C-type lectins- that act through different mechanisms leading to the inhibition of the growth of bacteria, as well as, cytotoxic effects and inhibition of metastasis process. In this review, we provide an overview of the venom toxins produced by species belonging to the Viperidae family, exploring their roles during the envenoming and their pharmacological properties, in order to demonstrate its antibacterial and antitumor potential.


Assuntos
Toxinas Biológicas , Viperidae , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Desintegrinas , Humanos , Venenos de Víboras/farmacologia
14.
Toxins (Basel) ; 14(2)2022 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-35202182

RESUMO

The venomous species Deinagkistrodon acutus has been used as anti-inflammatory medicine in China for a long time. It has been proven to have anti-inflammatory activity, but its specific anti-inflammatory components have not yet been fully elucidated. Tumor necrosis factor receptor-1 (TNFR1), which participates in important intracellular signaling pathways, mediates apoptosis, and functions as a regulator of inflammation, is often used as the target to develop anti-inflammatory drugs. The small peptides of snake venom have the advantages of weak immunogenicity and strong activity. To obtain the specific TNFR1 binding peptides, we constructed a T7 phage library of D. acutus venom glands, and then performed biopanning against TNFR1 on the constructed library. After biopanning three times, several sequences with potential binding capacity were obtained and one 41-amino acid peptide was selected through a series of biological analyses including sequence length, solubility, and simulated affinity, named DAvp-1. After synthesis, the binding capacity of DAvp-1 and TNFR1 was verified using surface plasmon resonance technology (SPR). Conclusively, by applying phage display technology, this work depicts the successful screening of a promising peptide DAvp-1 from D. acutus venom that binds to TNFR1. Additionally, our study emphasizes the usefulness of phage display technology for studies on screening natural product components.


Assuntos
Anti-Inflamatórios/análise , Técnicas de Visualização da Superfície Celular/métodos , Biblioteca de Peptídeos , Receptores Tipo I de Fatores de Necrose Tumoral/análise , Proteínas Recombinantes de Fusão/análise , Venenos de Serpentes/química , Viperidae , Animais , China
15.
PLoS One ; 17(2): e0263238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35180240

RESUMO

BACKGROUND: Envenomation by the European adder, Vipera berus berus (Vbb), is a medical emergency. The overall in vivo haemostatic effects of pro- and anticoagulant components in Vbb venom, and the downstream effects of cellular injury and systemic inflammation, are unclear. OBJECTIVES: To longitudinally describe the global coagulation status of dogs after Vbb envenomation and compare to healthy controls. A secondary aim was to investigate differences between dogs treated with and without antivenom. METHODS: Citrated plasma was collected at presentation, 12 hours (h), 24 h, 36 h and 15 days after bite from 28 dogs envenomated by Vbb, and from 28 healthy controls at a single timepoint. Thrombin generation (initiated with and without exogenous phospholipids and tissue factor), thrombin-antithrombin (TAT)-complexes and the procoagulant activity of phosphatidylserine (PS)-expressing extracellular vesicles (EVs), expressed as PS-equivalents, were measured. RESULTS: At presentation the envenomated dogs were hypercoagulable compared to controls, measured as increased thrombin generation, TAT-complexes and PS-equivalents. The hypercoagulability decreased gradually but compared to controls thrombin generation and PS-equivalents were still increased at day 15. The discrepancy in peak thrombin between envenomated dogs and controls was greater when the measurement was phospholipid-dependent, indicating that PS-positive EVs contribute to hypercoagulability. Lag time was shorter in non-antivenom treated dogs, compared to antivenom treated dogs <24 h after envenomation. CONCLUSIONS: Hypercoagulability was measured in dogs up to 15 days after Vbb envenomation. Dogs treated with antivenom may be less hypercoagulable than their non-antivenom treated counterparts. Thrombin generation is a promising diagnostic and monitoring tool for Vbb envenomation.


Assuntos
Antivenenos/uso terapêutico , Doenças do Cão/etiologia , Doenças do Cão/terapia , Fatores Imunológicos/uso terapêutico , Mordeduras de Serpentes/complicações , Trombofilia/etiologia , Trombofilia/veterinária , Viperidae , Animais , Antitrombina III , Estudos de Casos e Controles , Cães , Feminino , Inflamação/sangue , Inflamação/etiologia , Inflamação/terapia , Inflamação/veterinária , Estudos Longitudinais , Masculino , Peptídeo Hidrolases/sangue , Trombina/análise , Trombofilia/sangue , Trombofilia/terapia , Resultado do Tratamento , Venenos de Víboras/imunologia
16.
PLoS Negl Trop Dis ; 16(2): e0010148, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35139079

RESUMO

BACKGROUND: Millions of people are bitten by venomous snakes annually, causing high mortality and disability, but the true burden of this neglected health issue remains unknown. Since 2015, Médecins Sans Frontières has been treating snakebite patients in a field hospital in north-west Ethiopia. Due to the poor market situation for effective and safe antivenoms for Sub-Saharan Africa, preferred antivenom was not always available, forcing changes in choice of antivenom used. This study describes treatment outcomes and the effectiveness and safety of different antivenoms used. METHODOLOGY / PRINCIPAL FINDINGS: This retrospective observational study included 781 snakebite patients presenting at the field hospital between 2015 and 2019. Adjusted odds ratios, 95%-CI and p-values were used to compare the treatment outcome of patients treated with Fav-Afrique (n = 149), VacSera (n = 164), and EchiTAb-PLUS-ICP (n = 156) antivenom, and to identify the risk of adverse reactions for each antivenom. Whereas only incidental snakebite cases presented before 2015, after treatment was made available, cases rapidly increased to 1,431 in 2019. Envenomation was mainly attributed to North East African saw-scaled viper (Echis pyramidum) and puff adder (Bitis arietans). Patients treated with VacSera antivenom showed lower chance of uncomplicated treatment outcome (74.4%) compared to Fav-Afrique (93.2%) and EchiTAb-PLUS-ICP (90.4%). VacSera and EchiTAb-PLUS-ICP were associated with 16- and 6-fold adjusted odds of treatment reaction compared to Fav-Afrique, respectively, and VacSera was weakly associated with higher odds of death. CONCLUSIONS / SIGNIFICANCE: Snakebite frequency is grossly underreported unless treatment options are available. Although EchiTAb-PLUS-ICP showed favorable outcomes in this retrospective analysis, prospective randomized trials are needed to evaluate the effectiveness and safety of the most promising antivenoms for Sub-Saharan Africa. Structural investment in sustained production and supply of antivenom is urgently needed.


Assuntos
Antivenenos/uso terapêutico , Mordeduras de Serpentes/tratamento farmacológico , Adolescente , Adulto , Idoso , Animais , Antivenenos/efeitos adversos , Criança , Pré-Escolar , Etiópia/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Mordeduras de Serpentes/epidemiologia , Mordeduras de Serpentes/mortalidade , Mordeduras de Serpentes/parasitologia , Resultado do Tratamento , Viperidae/fisiologia , Adulto Jovem
17.
Am J Trop Med Hyg ; 106(3): 967-969, 2022 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-35100564

RESUMO

Snakebite envenoming is a common occupational hazard in the tropics. Venom-induced consumption coagulopathy and acute kidney injury are the most frequently encountered complications of viper bites. Diffuse alveolar hemorrhage (DAH) is an unusual presentation reported rarely in the literature. Our case report highlights the uncommon presentation of delayed pulmonary hemorrhage after snakebite envenoming. A 40-year-old healthy man presented to our emergency department after 6 hours of Echis sochureki (a saw-scaled viper subspecies) bite. He had abnormal coagulation parameters and thrombocytopenia with no signs of acute kidney injury. Transfusion protocols were initiated because of active bleeding and a rapid decrease in hemoglobin levels over next few days. Around day 10, his coagulation profile and hemoglobin were corrected, but he developed hemoptysis with rapidly progressive respiratory distress. Computed tomography of the chest was suggestive of DAH and the patient was started on plasma exchange with pulse methylprednisolone. After the initial worsening, he had rapid symptomatic improvement and radiological resolution. The patient had persistent hypofibrinogenemia, which resolved, and was discharged and remained healthy at the 60-day follow-up. This case highlights a presentation with an initial phase of venom-induced consumption coagulopathy followed by delayed DAH in saw-scaled viper envenoming that was treated successfully with immunosuppressants and plasma exchange.


Assuntos
Injúria Renal Aguda , Coagulação Intravascular Disseminada , Mordeduras de Serpentes , Viperidae , Adulto , Animais , Antivenenos , Feminino , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Masculino , Mordeduras de Serpentes/complicações , Mordeduras de Serpentes/terapia , Venenos de Víboras/toxicidade
18.
Toxicon ; 207: 48-51, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34995557

RESUMO

Latifi's viper (Montivipera latifii), also known as Lar Valley or Damavandi viper, is endemic to Iran. It has rarely been recorded, as it occurs in a highly-protected national park. In this first clinical report of a confirmed bite by this species, a teenage girl was bitten on the chin, causing rapidly-progressive swelling of the face and oropharyngeal mucosa. At a local hospital, a misleading history given by the patient's relatives of a wasp sting and inadequate inspection of the bite wound misled the physicians from making the correct diagnosis, resulting in a considerable delay in the administration of antivenom. This allowed the development of partial obstruction of the upper airway causing respiratory distress. After transfer to a tertiary hospital, attempts at endotracheal intubation failed, necessitating tracheostomy, but this was not implemented early enough to prevent her developing respiratory failure and losing consciousness. After she was stabilized, snakebite envenoming was diagnosed by a clinical toxicologist who observed two fang puncture marks on her chin. This was later confirmed when a snake, identified as M. latifii, was discovered at the room where the bite had occurred. Her facial swelling and ecchymosis, attributable to envenoming, were effectively controlled by high-dose antivenom therapy. However, she did not recover consciousness, remaining in a vegetative state. About three weeks after the bite, she died as an indirect result of hypoxic brain damage complicated by septicemia. Prompt diagnosis, relief of upper airway obstruction and timely antivenom therapy might have prevented this tragic fatal outcome.


Assuntos
Mordeduras de Serpentes , Viperidae , Adolescente , Animais , Antivenenos/uso terapêutico , Feminino , Humanos , Mordeduras de Serpentes/tratamento farmacológico , Venenos de Víboras/envenenamento
19.
Toxicon ; 208: 18-30, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35026216

RESUMO

The epidemiology features and clinical symptoms associated with 121 cases of snakebite requiring admission to 24 hospitals in Jordan, during 2018-2020, are discussed. Ninety-six of them (79%) brought with them to the hospital the snake that bit them or a photograph of it. Echis coloratus was responsible for 68 of the bites and 6 fatalities. Sex ratio was 3.2 males: 1 female, with an overall average age of 27 ± 14.36 years. The highest incidence of bites was reported in September. Bites were most common on hands and legs. The period of hospitalization ranged from 1 to 36 days. Irbid and Karak governorates had the highest number of snakebites, most cases being reported from agricultural areas and among farmers. Clinical symptoms associated with five species of venomous snakes are described along with illustrative case histories. Symptoms associated with Echis coloratus bites included local swelling and necrosis, coagulopathy and bleeding, microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) and chronic renal failure. Daboia palaestinae victims exhibited ecchymoses, local swelling and necrosis, with one case of angioedema. Other symptoms included thrombocytopenia, coagulopathy, microangiopathic hemolysis and local and systemic bleeding, as well as AKI. A single case of envenoming by Macrovipera lebetinus developed the following symptoms; swelling, severe pain, extensive ecchymoses, neutrophil leukocytosis, normochromic normocytic anemia and aggregated platelets with thrombocytopenia. Symptoms associated with two cases of Pseudocerastes fieldi included swelling that spread from bitten hands, and mild abnormalities of platelet count and bleeding time. Four cases of envenoming by Atractaspis engaddensis exhibited severe pain, local swelling, erythema, numbness and tissue necrosis. One of them developed acute systemic symptoms. The only antivenom currently available in Jordan, is VINS "Snake venom antitoxin (Biosnake)", manufactured in India using venoms of three African snakes that do not occur in Jordan. It proved clinically ineffective against envenoming by Jordanian Viperidae, failing to correct coagulopathy and life-threatening hemorrhage, and to prevent AKI.


Assuntos
Mordeduras de Serpentes , Viperidae , Adolescente , Adulto , Animais , Antivenenos/uso terapêutico , Criança , Estudos Epidemiológicos , Feminino , Humanos , Jordânia/epidemiologia , Masculino , Mordeduras de Serpentes/tratamento farmacológico , Mordeduras de Serpentes/epidemiologia , Adulto Jovem
20.
Top Companion Anim Med ; 46: 100586, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34583053

RESUMO

Dogs are commonly bitten by the European adder (Vipera berus) but studies investigating the effects of envenomation are limited. Snakebite-related kidney injury is reported in dogs but diagnosis of acute kidney injury (AKI) might be limited by the insensitivity of routinely used renal function biomarkers. The aim of this study was to evaluate novel biomarkers of renal injury (urinary cystatin B and urinary clusterin) and biomarkers of renal function (serum creatinine and serum symmetric dimethylarginine), and urine protein to creatinine ratio in dogs envenomated by V. berus. Biomarkers were measured at presentation (T1), 12 hours (T2), 24 hours (T3), 36 hours (T4), and 14 days (T5) after snakebite and compared to a group of healthy control dogs. A secondary aim was to investigate the association between biomarker concentrations and severity of clinical signs of envenomation using a snakebite severity score (SSS). Urinary cystatin B concentrations were significantly higher at all timepoints in envenomated dogs compared to controls (P < .010), except for T5 (P = .222). Absolute urinary clusterin concentrations were not significantly different to controls at any timepoint. Compared to controls, serum creatinine and serum symmetric dimethylarginine concentrations were significantly lower in envenomated dogs at T1-T4 (P < .036) and T2-T4 (P < .036), respectively. Urine protein to creatinine ratio was higher in envenomated dogs compared to controls at T2 and T3. Urinary cystatin B concentrations at T1 were correlated with SSS (Spearman's ρ = 0.690, P < .001). The increased urinary cystatin B concentrations observed in dogs envenomated by V. berus in comparison to controls may indicate renal tubular injury in these patients.


Assuntos
Doenças do Cão , Viperidae , Animais , Biomarcadores , Clusterina , Cistatina B , Doenças do Cão/diagnóstico , Cães , Rim/fisiologia
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