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1.
Nucleic Acids Res ; 52(10): 6049-6065, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38709882

RESUMEN

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a human pathogen that is now endemic to several East Asian countries. The viral large (L) protein catalyzes viral transcription by stealing host mRNA caps via a process known as cap-snatching. Here, we establish an in vitro cap-snatching assay and present three high-quality electron cryo-microscopy (cryo-EM) structures of the SFTSV L protein in biologically relevant, transcription-specific states. In a priming-state structure, we show capped RNA bound to the L protein cap-binding domain (CBD). The L protein conformation in this priming structure is significantly different from published replication-state structures, in particular the N- and C-terminal domains. The capped-RNA is positioned in a way that it can feed directly into the RNA-dependent RNA polymerase (RdRp) ready for elongation. We also captured the L protein in an early-elongation state following primer-incorporation demonstrating that this priming conformation is retained at least in the very early stages of primer extension. This structural data is complemented by in vitro biochemical and cell-based assays. Together, these insights further our mechanistic understanding of how SFTSV and other bunyaviruses incorporate stolen host mRNA fragments into their viral transcripts thereby allowing the virus to hijack host cell translation machinery.


Asunto(s)
Interacciones Microbiota-Huesped , Modelos Moleculares , Phlebovirus , Caperuzas de ARN , Transcripción Genética , Humanos , Microscopía por Crioelectrón , Phlebovirus/química , Phlebovirus/genética , Phlebovirus/ultraestructura , Conformación Proteica , Caperuzas de ARN/química , Caperuzas de ARN/metabolismo , Caperuzas de ARN/ultraestructura , ARN Viral/química , ARN Viral/metabolismo , ARN Polimerasa Dependiente del ARN/metabolismo , Proteínas Virales/química , Proteínas Virales/metabolismo , Proteínas Virales/ultraestructura , Replicación Viral/fisiología , Interacciones Microbiota-Huesped/fisiología
2.
Toxins (Basel) ; 16(5)2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38787074

RESUMEN

Snakebite envenoming and its resulting complications are serious threats to the health of vulnerable people living in rural areas of developing countries. The knowledge of the heterogeneity of symptoms associated with snakebite envenoming and their management strategies is vital to treat such life-threatening complications to save lives. Russell's viper envenomation induces a diverse range of clinical manifestations from commonly recognised haemotoxic and local effects to several rare conditions that are often not reported. The lack of awareness about these unusual manifestations can affect prompt diagnosis, appropriate therapeutic approaches, and positive outcomes for patients. Here, we report pulmonary thromboembolism that developed in three patients following Russell's viper envenomation and demonstrate their common clinical features and diagnostic and therapeutic approaches used. All patients showed clinical signs of local (oedema) and systemic (blood coagulation disturbances) envenomation, which were treated using polyvalent antivenom. They exhibited elevated heart rates, breathlessness, and reduced oxygen saturation, which are non-specific but core parameters in the diagnosis of pulmonary embolism. The recognition of pulmonary embolism was also achieved by an electrocardiogram, which showed sinus tachycardia and computed tomography and echocardiogram scans further confirmed this condition. Anti-coagulant treatment using low-molecular-weight heparin offered clinical benefits in these patients. In summary, this report reinforces the broad spectrum of previously unreported consequences of Russell's viper envenomation. The constant updating of healthcare professionals and the dissemination of major lessons learned in the clinical management of snakebite envenoming through scientific documentation and educational programs are necessary to mitigate the adverse impacts of venomous snakebites in vulnerable communities.


Asunto(s)
Antivenenos , Daboia , Embolia Pulmonar , Mordeduras de Serpientes , Mordeduras de Serpientes/complicaciones , Mordeduras de Serpientes/tratamiento farmacológico , Embolia Pulmonar/etiología , Embolia Pulmonar/tratamiento farmacológico , Humanos , Animales , Masculino , Antivenenos/uso terapéutico , Venenos de Víboras/toxicidad , Adulto , Femenino , Persona de Mediana Edad , Anticoagulantes/uso terapéutico
4.
J Biol Chem ; 300(1): 105552, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38072065

RESUMEN

Fibrinogen C domain-containing protein 1 (FIBCD1) is an immune protein proposed to be involved in host recognition of chitin on the surface of pathogens. As FIBCD1 readily binds acetylated molecules, we have determined the high-resolution crystal structures of a recombinant fragment of the FIBCD1 C-terminal domain complexed with small N-acetyl-containing ligands to determine the mode of recognition. All ligands bind at the conserved N-acetyl-binding site (S1) with galactose and glucose-derived ligands rotated 180° relative to each other. One subunit of a native structure derived from protein expressed in mammalian cells binds glycosylation from a neighboring subunit, in an extended binding site. Across the various structures, the primary S1 binding pocket is occupied by N-acetyl-containing ligands or acetate, with N-acetyl, acetate, or sulfate ion in an adjacent pocket S1(2). Inhibition binding studies of N-acetylglucosamine oligomers, (GlcNAc)n, n = 1, 2, 3, 5, 11, via ELISA along with microscale thermophoresis affinity assays indicate a strong preference of FIBCD1 for longer N-acetylchitooligosaccharides. Binding studies of mutant H396A, located beyond the S1(2) site, showed no significant difference from wildtype, but K381L, within the S1(2) pocket, blocked binding to the model ligand acetylated bovine serum albumin, suggesting that S1(2) may have functional importance in ligand binding. The binding studies, alongside structural definition of diverse N-acetyl monosaccharide binding in the primary S1 pocket and of additional, adjacent binding pockets, able to accommodate both carbohydrate and sulfate functional groups, suggest a versatility in FIBCD1 to recognize chitin oligomers and other pathogen-associated carbohydrate motifs across an extended surface.


Asunto(s)
Receptores de Superficie Celular , Humanos , Acetatos , Sitios de Unión/fisiología , Carbohidratos/química , Quitina/metabolismo , Hemostáticos , Ligandos , Unión Proteica , Receptores de Superficie Celular/química , Receptores de Superficie Celular/metabolismo , Sulfatos , Modelos Moleculares , Estructura Terciaria de Proteína
5.
J Am Chem Soc ; 145(51): 27958-27974, 2023 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-38104324

RESUMEN

Lassa virus is a negative-strand RNA virus with only four structural proteins that causes periodic outbreaks in West Africa. The nucleoprotein (NP) encapsidates the viral genome, forming ribonucleoprotein complexes (RNPs) together with the viral RNA and the L protein. RNPs must be continuously restructured during viral genome replication and transcription. The Z protein is important for membrane recruitment of RNPs, viral particle assembly, and budding and has also been shown to interact with the L protein. However, the interaction of NP, viral RNA, and Z is poorly understood. Here, we characterize the interactions between Lassa virus NP, Z, and RNA using structural mass spectrometry. We identify the presence of RNA as the driver for the disassembly of ring-like NP trimers, a storage form, into monomers to subsequently form higher order RNA-bound NP assemblies. We locate the interaction site of Z and NP and demonstrate that while NP binds Z independently of the presence of RNA, this interaction is pH-dependent. These data improve our understanding of RNP assembly, recruitment, and release in Lassa virus.


Asunto(s)
Virus Lassa , Ribonucleoproteínas , Virus Lassa/genética , Virus Lassa/metabolismo , Ribonucleoproteínas/química , Nucleoproteínas , Ensamble de Virus , ARN Viral/genética , ARN Viral/metabolismo
6.
PLoS Negl Trop Dis ; 17(10): e0011699, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37844081

RESUMEN

BACKGROUND: India suffers ~58,000 annual deaths due to snakebites. The 'Big Four' snakes (Russell's viper, Indian cobra, common krait, and saw-scaled viper) that are responsible for most bites cause diverse clinical effects. Delayed treatment increases the risk of serious complications and treatment costs. Although government hospitals offer free treatment for snakebites in India, most patients opt for private healthcare, which is an out-of-pocket expense as they often lack health insurance coverage. This study aims to analyse snakebite treatment costs in private tertiary care hospitals in Tamil Nadu, India and identifies the key factors contributing to treatment costs. METHODOLOGY/PRINCIPAL FINDINGS: The treatment cost details for 913 snakebite victims were collected from 10 private tertiary care hospitals across Tamil Nadu. The data were classified into hospital, pharmacy, investigation, and laboratory costs, and analysed to determine various factors that contribute to the costs. The results demonstrate that the average treatment costs vary widely for different snakes. The hospital and pharmacy costs are higher than investigation and laboratory costs for all snakebites. Notably, Russell's viper bites cost significantly more than the bites from other snakes. Overall, the type of snake, nature of complications, specialist treatments required, and arrival time to hospitals were identified as some of the key factors for higher treatment costs. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that ~80% of snakebite patients can be treated with INR 100,000 (~GBP 1000 or USD 1200) or less. This study emphasises the urgent need to improve rural medical care by providing appropriate training for healthcare professionals and essential resources to facilitate early assessment of patients, administer the initial dose of antivenom and refer the patients to tertiary care only when needed. Moreover, the outcome of this study forms a basis for developing appropriate policies to regulate snakebite treatment costs and provide affordable medical insurance for vulnerable communities.


Asunto(s)
Daboia , Mordeduras de Serpientes , Viperidae , Animales , Humanos , Mordeduras de Serpientes/tratamiento farmacológico , Atención Terciaria de Salud , India/epidemiología , Antivenenos/uso terapéutico , Costos de la Atención en Salud
7.
Toxins (Basel) ; 15(9)2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37755956

RESUMEN

The interactions between specific snake venom toxins and muscle constituents are the major cause of severe muscle damage that often result in amputations and subsequent socioeconomic ramifications for snakebite victims and/or their families. Therefore, improving our understanding of venom-induced muscle damage and determining the underlying mechanisms of muscle degeneration/regeneration following snakebites is critical to developing better strategies to tackle this issue. Here, we analysed intramuscular bleeding and thrombosis in muscle injuries induced by two different snake venom toxins (CAMP-Crotalus atrox metalloprotease (a PIII metalloprotease from the venom of this snake) and a three-finger toxin (CTX, a cardiotoxin from the venom of Naja pallida)). Classically, these toxins represent diverse scenarios characterised by persistent muscle damage (CAMP) and successful regeneration (CTX) following acute damage, as normally observed in envenomation by most vipers and some elapid snakes of Asian, Australasian, and African origin, respectively. Our immunohistochemical analysis confirmed that both CAMP and CTX induced extensive muscle destruction on day 5, although the effects of CTX were reversed over time. We identified the presence of fibrinogen and P-selectin exposure inside the damaged muscle sections, suggesting signs of bleeding and the formation of platelet aggregates/microthrombi in tissues, respectively. Intriguingly, CAMP causes integrin shedding but does not affect any blood clotting parameters, whereas CTX significantly extends the clotting time and has no impact on integrin shedding. The rates of fibrinogen clearance and reduction in microthrombi were greater in CTX-treated muscle compared to CAMP-treated muscle. Together, these findings reveal novel aspects of venom-induced muscle damage and highlight the relevance of haemostatic events such as bleeding and thrombosis for muscle regeneration and provide useful mechanistic insights for developing better therapeutic interventions.


Asunto(s)
Crotalus , Mordeduras de Serpientes , Trombosis , Serpientes Venenosas , Humanos , Cardiotoxinas/toxicidad , Venenos Elapídicos/farmacología , Venenos de Serpiente/farmacología , Hemorragia/inducido químicamente , Metaloproteasas/farmacología , Fibrinógeno , Músculo Esquelético , Integrinas , Mordeduras de Serpientes/complicaciones
8.
Toxicon ; 234: 107284, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37683700

RESUMEN

Snakebite envenoming (SBE) is common in rural communities living in tropical regions that often have fragile and/or overwhelmed healthcare systems. The complex scenarios around SBE lead to a high number of deaths, disabilities, and long-term consequences in patients. Russell's viper (Daboia russelii) is one of the most medically important snake species in India, which causes devastating pathological conditions characterised by a wide range of clinical manifestations. This broad spectrum of symptoms requires additional therapeutic interventions beyond the classical antivenom administration. Hence, positive outcomes for patients affected by SBE can be achieved with a better understanding of previous experiences describing clinical manifestations and various therapeutic interventions including for rare and underreported conditions. Here, we report an SBE victim who developed partial segmental thrombosis in the corpus cavernosum following Russell's viper envenomation and its diagnostic and treatment approaches. The patients received 180 ml of antivenom to resolve the abnormalities in their haematological parameters. Despite antivenom treatment, they developed severe pain in their genital region, and subsequent ultrasound and magnetic resonance imaging confirmed segmental thrombosis in the corpus cavernosum, which required supportive measures. The treatment using low molecular weight heparin, rivaroxaban and non-steroidal anti-inflammatory drugs resolved segmental thrombosis. In conclusion, this case report exemplifies the development of a rare segmental thrombosis in corpus cavernosum and how the medical, scientific, and general community can benefit from documenting clinical manifestations, medically relevant insights into patient care and the management of underreported complications.

9.
TH Open ; 7(2): e168-e183, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37333023

RESUMEN

Envenomings by Russell's viper ( Daboia russelii ), a species of high medical importance in India and other Asian countries, commonly result in hemorrhage, coagulopathies, necrosis, and acute kidney injury. Although bleeding complications are frequently reported following viper envenomings, thrombotic events occur rarely (reported only in coronary and carotid arteries) with serious consequences. For the first time, we report three serious cases of peripheral arterial thrombosis following Russell's viper bites and their diagnostic, clinical management, and mechanistic insights. These patients developed occlusive thrombi in their peripheral arteries and symptoms despite antivenom treatment. In addition to clinical features, computed tomography angiography was used to diagnose arterial thrombosis and ascertain its precise locations. They were treated using thrombectomy or amputation in one case that presented with gangrenous digits. Mechanistic insights into the pathology through investigations revealed the procoagulant actions of Russell's viper venom in standard clotting tests as well as in rotational thromboelastometry analysis. Notably, Russell's viper venom inhibited agonist-induced platelet activation. The procoagulant effects of Russell's viper venom were inhibited by a matrix metalloprotease inhibitor, marimastat, although a phospholipase A 2 inhibitor (varespladib) did not show any inhibitory effects. Russell's viper venom induced pulmonary thrombosis when injected intravenously in mice and thrombi in the microvasculature and affected skeletal muscle when administered locally. These data emphasize the significance of peripheral arterial thrombosis in snakebite victims and provide awareness, mechanisms, and robust strategies for clinicians to tackle this issue in patients.

10.
PLoS Negl Trop Dis ; 17(4): e0011264, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37099489

RESUMEN

With the continued growth of human populations, rural urbanisation and habitat degradation are on the rise, resulting in the displacement of native wildlife and an increase in human-wildlife conflicts. The presence of human habitation and waste often attracts rodents and thereby, snakes, leading to increased snake sightings in homes. To address this problem, snake handlers, who are volunteers that remove and relocate snakes away from human development areas, are called upon. However, snake removal is a high-risk task that poses a risk of envenomation, particularly when dealing with spitting snakes. Several cobra species have the ability to spit venom. If the venom enters a person's eye, it can result in ophthalmic envenomation, which can have serious consequences for their eyesight. Therefore, snake handlers should take precautions, wear suitable eye protection, and use appropriate tools to ensure their safety and that of the snake. In this case, an experienced snake handler was called to remove a spitting cobra, but they were ill-equipped. During the removal, the venom was sprayed across the handler's face, and some of it entered their eye, resulting in ophthalmic envenomation. The handler promptly irrigated their eye, but medical treatment was still necessary. This report highlights the risks and consequences of ophthalmic injury and the importance of wearing appropriate eye protection and taking due care when dealing with venomous species, particularly those that can spit venom. It serves as a reminder that accidents can happen at any time and experienced snake handlers are not exempt from the risks.


Asunto(s)
Mordeduras de Serpientes , Animales , Humanos , Mordeduras de Serpientes/terapia , Elapidae , Venenos Elapídicos , Antivenenos , Venenos de Serpiente
11.
Toxicon ; 228: 107111, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37060927

RESUMEN

Snakebite envenomation is regarded as a high-priority neglected tropical disease by the World Health Organisation, as it results in significant loss of lives and permanent disabilities. Russell's viper is one of the important venomous snakes that causes morbidities, mortalities and disabilities in India. The clinical presentation of Russell's viper envenomation is characterised by local envenoming effects including tissue damage, venom-induced coagulopathy, neurotoxicity, and kidney injury. However, venom composition and its mechanisms of toxicity are highly variable even within snakes of the same species including Russell's viper. This variation in venom composition results in a broad range of clinical complications. Here, we present a previously undocumented case of neutrophil-mediated erythrophagocytosis in a healthy 28-year-old female following Russell's viper bite. Systemic envenomation effects and bleeding abnormalities in this patient were corrected by the administration of polyvalent antivenom. Two days later, the patient developed progressive swelling and ecchymosis in the bitten limb. Observed abnormal limits within blood testing were followed up by a peripheral blood smear where it was found that 30% of neutrophils had phagocytosed erythrocytes as they were found within the cytoplasm. The patient underwent a fasciotomy for compartmental syndrome and received packed red cells and a course of corticosteroids. Following this treatment, the patient made a full recovery. This case report outlines a previously undocumented pathological event induced by Russell's viper envenomation, guiding diagnosis and treatment. Clinicians' knowledge of the mechanisms of toxicity of Russell's viper envenomation and its clinical manifestations are essential for improving the treatment of snakebites to achieve positive outcomes.


Asunto(s)
Daboia , Mordeduras de Serpientes , Animales , Femenino , Neutrófilos , Venenos de Víboras/toxicidad , Mordeduras de Serpientes/tratamiento farmacológico , Antivenenos/uso terapéutico , Antivenenos/farmacología
12.
Toxins (Basel) ; 15(3)2023 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-36977081

RESUMEN

Snakebite envenomation (SBE) is a life-threatening medical emergency with a high mortality rate. Common secondary complications following SBE, such as wound infections, are significant due to their impact on worsening local tissue damage and causing systemic infection. Antivenoms are not effective to treat wound infections following SBE. Moreover, in several rural clinical settings, broad-spectrum antibiotics are often used without clear guidelines or based on limited laboratory data, resulting in undesirable side effects and exacerbated treatment costs. Therefore, robust antibiotic strategies should be developed to tackle this critical issue. Currently, there is limited information available on the bacterial profiles of SBE-induced infections and antibiotic susceptibility. Hence, it is essential to improve the knowledge of bacterial profiles and their antibiotic sensitivity in SBE victims to develop better treatment strategies. This study aimed to address this issue by examining the bacterial profiles of SBE victims with a specific focus on Russell's viper envenomation. The most frequently found bacteria in the bites of SBE victims were Staphylococcus aureus, Klebsiella sp., Escherichia coli, and Pseudomonas aeruginosa. Linezolid, clindamycin, colistin, meropenem, and amikacin were some of the most effective antibiotics for commonly grown bacteria in SBE victims. Similarly, ciprofloxacin, ampicillin, amoxiclave, cefixime, and tetracyclin were the least effective antibiotics for common bacteria found in the wound swabs of SBE victims. These data provide robust guidance for infection management following SBE and offer useful insights to aid in designing effective treatment protocols for SBE with serious wound infections in rural areas where laboratory facilities may not be readily available.


Asunto(s)
Infecciones Bacterianas , Mordeduras de Serpientes , Humanos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Antivenenos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Mordeduras de Serpientes/complicaciones , Venenos de Víboras/uso terapéutico
13.
Toxicon ; 225: 107068, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36863530

RESUMEN

The clinical management of snakebite envenomation (SBE) is challenging in many tropical and subtropical regions of developing countries due to the complex clinical manifestations and inadequate medical infrastructure. Some venomous snakes, such as the Indian Russell's viper (Daboia russelii) cause a wide range of rare complications in addition to their classical envenomation effects. In general, these uncommon complications are often misdiagnosed or not treated promptly due to a lack of awareness about these conditions. Thus, it is critical to report such complications to draw the attention of the healthcare and research communities to improve the clinical management and scientific research of SBE, respectively. Here, we report bilateral adrenal and pituitary haemorrhages in an SBE patient following a bite by Russell's viper in India. The initial symptoms included gum bleeding, swelling, axillary lymphadenopathy and clotting abnormalities. Despite the administration of antivenom, the patient presented palpitation, nausea, and abdominal pain, which were not recovered by combinational therapy with epinephrine and dexamethasone. Further infusion of antivenom did not address these issues and the patient displayed persistent hypotension, hypoglycaemia and hyperkalaemia suggesting an adrenal crisis. Inadequate secretion of corticosteroids was confirmed by laboratory tests, and imaging investigations revealed haemorrhages in both the adrenal and pituitary glands. The patient made a full recovery after treatment with hydrocortisone and thyroxine. This report adds to the growing evidence of rare complications induced by Russell's viper envenomations and it provides relevant guidance to diagnose and treat such complications in SBE victims.


Asunto(s)
Daboia , Mordeduras de Serpientes , Animales , Antivenenos/uso terapéutico , Venenos de Víboras , Mordeduras de Serpientes/tratamiento farmacológico , India
14.
PLoS Pathog ; 19(1): e1011060, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36634042

RESUMEN

Bunyaviruses are negative sense, single-strand RNA viruses that infect a wide range of vertebrate, invertebrate and plant hosts. WHO lists three bunyavirus diseases as priority diseases requiring urgent development of medical countermeasures highlighting their high epidemic potential. While the viral large (L) protein containing the RNA-dependent RNA polymerase is a key enzyme in the viral replication cycle and therefore a suitable drug target, our knowledge on the structure and activities of this multifunctional protein has, until recently, been very limited. However, in the last few years, facilitated by the technical advances in the field of cryogenic electron microscopy, many structures of bunyavirus L proteins have been solved. These structures significantly enhance our mechanistic understanding of bunyavirus genome replication and transcription processes and highlight differences and commonalities between the L proteins of different bunyavirus families. Here, we provide a review of our current understanding of genome replication and transcription in bunyaviruses with a focus on the viral L protein. Further, we compare within bunyaviruses and with the related influenza virus polymerase complex and highlight open questions.


Asunto(s)
Bunyaviridae , Orthobunyavirus , Bunyaviridae/genética , Bunyaviridae/metabolismo , Orthobunyavirus/genética , ARN , Proteínas Virales/genética , Proteínas Virales/metabolismo , Replicación Viral/genética
15.
Nucleic Acids Res ; 51(3): 1424-1442, 2023 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-36651274

RESUMEN

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a phenuivirus that has rapidly become endemic in several East Asian countries. The large (L) protein of SFTSV, which includes the RNA-dependent RNA polymerase (RdRp), is responsible for catalysing viral genome replication and transcription. Here, we present 5 cryo-electron microscopy (cryo-EM) structures of the L protein in several states of the genome replication process, from pre-initiation to late-stage elongation, at a resolution of up to 2.6 Å. We identify how the L protein binds the 5' viral RNA in a hook-like conformation and show how the distal 5' and 3' RNA ends form a duplex positioning the 3' RNA terminus in the RdRp active site ready for initiation. We also observe the L protein stalled in the early and late stages of elongation with the RdRp core accommodating a 10-bp product-template duplex. This duplex ultimately splits with the template binding to a designated 3' secondary binding site. The structural data and observations are complemented by in vitro biochemical and cell-based mini-replicon assays. Altogether, our data provide novel key insights into the mechanism of viral genome replication by the SFTSV L protein and will aid drug development against segmented negative-strand RNA viruses.


Asunto(s)
Phlebovirus , Síndrome de Trombocitopenia Febril Grave , Humanos , Síndrome de Trombocitopenia Febril Grave/genética , Microscopía por Crioelectrón , ARN Viral/genética , ARN Polimerasa Dependiente del ARN/metabolismo , Phlebovirus/genética , Replicación Viral , Genoma Viral
16.
Toxicon ; 224: 107037, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36690089

RESUMEN

Snakebite envenomation causes systemic and local manifestations, which result from the individual or synergistic actions of multiple venom components. The pathological hallmarks of medically important venomous snakes such as the Indian Russell's viper (Daboia russelii) are well known. Envenomation by Russell's viper is typically characterised by coagulopathies, muscular damage, nephrotoxicity, and neurotoxicity. However, recent reports have revealed several unusual complications that provide a better understanding of Russell's viper envenomation effects. To further strengthen this, here, we report a case of Russell's viper bite that induced acute abdominal pain, which was intensified on day two and conservatively treated under medical supervision. Both Fothergill and Carnett signs were positive for this patient. An ultrasound imaging revealed a dissimilar dense mass, and the abdominal computed tomography scan confirmed rectus sheath haematoma. The clinical management involved the administration of polyvalent antivenom, packed red blood cells, fresh frozen plasma, and platelets. The patient recovered gradually and was discharged from the hospital eight days after the bite. Overall, this case presentation shares an uncommon experience and adds new insights into the complex series of rare pathological events associated with Russell's viper bites in India. The scientific documentation of relatively infrequent entities based on an ongoing living assessment of medical experiences, for example, this rectus sheath haematoma, constitutes valuable guidance for an adequate diagnosis and timely treatment. Essential awareness among clinicians and further research on understanding the molecular relationship between Russell's viper venom and rectus sheath haematoma will improve patient outcomes and understanding of this condition, respectively.


Asunto(s)
Daboia , Síndromes de Neurotoxicidad , Mordeduras de Serpientes , Animales , Mordeduras de Serpientes/tratamiento farmacológico , Antivenenos/uso terapéutico , Venenos de Víboras , Síndromes de Neurotoxicidad/tratamiento farmacológico
17.
Toxins (Basel) ; 14(12)2022 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-36548714

RESUMEN

India suffers the highest incidence of snakebite envenomation (SBE) in the world. Rural communities within India and other countries have long-held cultural beliefs surrounding snakes and SBE treatments, with snake statues present in numerous Hindu temples. While most cultural beliefs are well respected and do not affect anyone, some people worship live venomous snakes without any safety precautions. Moreover, they practice various inappropriate first aid and traditional treatments that exacerbate SBE-induced complications. We report an unusual case of SBE on the tongue of a patient who was bitten while worshipping Russell's viper following the advice of an astrologer based on the appearance of a snake in the patient's dream. Following the bite, the tongue was deeply incised by the priest as a first aid to mitigate SBE-induced complications. The patient suffered profuse bleeding and swelling of the tongue resulting in difficulties in intubating them. The patient regained consciousness after antivenom administration, intranasal ventilation, and blood removal from the mouth. The tongue underwent extensive surgery to restore movement and function. This report advises caution to those undertaking the extremely risky practice of worshipping live snakes and emphasises the urgent need to develop and enforce policies to mitigate such actions and educate rural communities.


Asunto(s)
Daboia , Mordeduras de Serpientes , Animales , Primeros Auxilios , Mordeduras de Serpientes/complicaciones , Mordeduras de Serpientes/terapia , Mordeduras de Serpientes/epidemiología , Antivenenos/uso terapéutico , Lengua , Venenos de Víboras
18.
Toxins (Basel) ; 14(11)2022 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-36422979

RESUMEN

In India, most snakebite envenomation (SBE) incidents are caused by the "Big Four" snakes which include Russell's viper, common krait, Indian cobra, and saw-scaled viper. Their common envenomation effects include neurotoxicity, myotoxicity, and coagulopathy. However, they also induce rare complications such as priapism, pseudoaneurysm, and sialolithiasis. Ocular manifestations such as optic neuritis develop rarely following envenomations by non-spitting snakes and they may cause temporary vision changes and blindness if untreated. While optic neuritis following Indian cobra envenomation has been reported previously, this was not encountered in victims of common kraits. Hence, for the first time, we report optic neuritis developed in a victim following envenomation by a common krait and compare its clinical features and diagnostic and therapeutic methods used with another case of optic neuritis in a victim of an Indian cobra bite. Both patients received antivenom treatment and made an initial recovery; however, optic neuritis developed several days later. The condition was diagnosed using ophthalmic examination together with computed tomography and/or magnetic resonance imaging methods. Due to very similar clinical features, both patients received intravenous corticosteroids which restored their vision and successfully treated optic neuritis. This case report suggests that the optic neuritis developed in a common krait envenomation is comparable to the one developed following a cobra bite, and therefore, the same diagnostic and therapeutic approaches can be used. This study also raises awareness of this rare complication and provides guidance for the diagnosis and treatment of SBE-induced optic neuritis.


Asunto(s)
Neuritis Óptica , Mordeduras de Serpientes , Masculino , Animales , Naja naja , Bungarus , Neuritis Óptica/diagnóstico , Neuritis Óptica/tratamiento farmacológico , Neuritis Óptica/etiología , Mordeduras de Serpientes/complicaciones , Mordeduras de Serpientes/diagnóstico , Mordeduras de Serpientes/tratamiento farmacológico , Antivenenos/uso terapéutico
19.
Toxicon ; 219: 106923, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36116739

RESUMEN

Snakebite envenomation is known to cause local as well as systemic haematological, myotoxic and neurological effects. Adverse effects on the endocrine system following envenomation are rarely reported. Hirata's disease, also known as insulin autoimmune syndrome (IAS) is a rare disorder that causes hypoglycaemia due to excessive production of insulin autoantibodies. This report describes a rare case of IAS which developed in a snakebite victim following envenomation by a common krait and antivenom treatment. The patient was initially treated with dextrose and corticosteroids, although plasmapheresis was required to reduce the concentration of insulin antibodies and normalise the patient's glucose level. The patient then made an uneventful recovery without permanent sequelae. This report demonstrates the impacts of envenomation by a common krait on developing Hirata's disease and creates awareness among clinicians who treat snakebite envenomation.


Asunto(s)
Enfermedades Autoinmunes , Insulinas , Mordeduras de Serpientes , Animales , Bungarus , Anticuerpos Insulínicos , Antivenenos/uso terapéutico , Mordeduras de Serpientes/complicaciones , Enfermedades Autoinmunes/etiología , Autoanticuerpos , Corticoesteroides , Glucosa
20.
Toxicon ; 215: 11-16, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35691405

RESUMEN

Snakebite envenomation is a high priority neglected tropical disease that predominantly affects rural communities living in developing countries. Due to myriad of complications including coagulopathies, neurotoxicity, nephrotoxicity and local tissue destruction, treating snakebite victims is a major challenge for clinicians. Russell's viper (Daboia russelii) is one of the 'Big Four' venomous snakes in India, and it is responsible for the most snakebite-induced deaths and disabilities. Acute kidney injury occurs frequently following Russell's viper bites and it is a critical factor contributing to disabilities, deaths and excessive treatment costs. In addition to commonly observed envenomation effects, Russell's viper bites induce some rare complications such as priapism, sialolithiasis and splenic rupture. Here, we report a case of Wunderlich syndrome that developed in a 22-year-old male following a Russell's viper bite. The patient displayed severe coagulopathies, abdominal tenderness, and hypotension. Notably, a peri-nephric haematoma was identified through ultrasound and computerised tomographic imaging. The haemorrhage was successfully treated using angioembolisation, and the patient recovered without any difficulties. Although a clinical condition such as this is rare, it is important to create awareness among treating clinicians about its occurrence, diagnosis and clinical management.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Daboia , Síndromes de Neurotoxicidad , Mordeduras de Serpientes , Adulto , Animales , Humanos , Masculino , Mordeduras de Serpientes/tratamiento farmacológico , Mordeduras de Serpientes/terapia , Venenos de Víboras/toxicidad , Adulto Joven
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