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Archives of Razi Institute Aug 2023(NNO) is one of the important venomous species in Iran. The current snakebite treatment is antivenom therapy that deals with hyper immunization of horses with crude or...
(NNO) is one of the important venomous species in Iran. The current snakebite treatment is antivenom therapy that deals with hyper immunization of horses with crude or fractionated snake venom plus traditional adjuvants, like Freund's adjuvant. For improvement of antivenom production, it has been suggested to use different adjuvant systems or immunization procedures. In this study, humoral immune responses against immunogenic fractions of NNO venom (NNO3 and NNO4) and crude venom have been compared by usage of different adjuvant and immunization routes. Additionally, a new indirect enzyme-linked immunosorbent assay (ELISA) was set up for the detection of specific antivenom antibodies. This study was conducted on six different groups of female Dutch rabbits that were hyperimmunized using crude and fractionated NNO venom, along with Freund's and MF59 adjuvants through subcutaneous or intramuscular route. The immunization was performed four times with 10-day intervals and the levels of specific antibodiees were detected by indirect ELISA. The statistical analysis reveals a negligible variation in the antivenom titers among the venom-inoculated groups, regardless of the adjuvant type or the immunization route. Finally, it was concluded that the fractions are efficient for antivenom production, and it is possible to use MF59 adjuvant via subcutaneous routes as an alternative to Freund's adjuvants considering its fair immunopotentiation capacity and safety in animals.
Topics: Female; Animals; Horses; Rabbits; Antivenins; Naja naja; Antibody Formation; Elapid Venoms; Adjuvants, Immunologic; Immunization; Freund's Adjuvant; Polysorbates; Squalene
PubMed: 38226391
DOI: 10.32592/ARI.2023.78.4.1177 -
F1000Research 2024On the 26 January 2023, a free to attend, 'improving snake venom research: a community discussion' meeting was held virtually. This webinar brought together...
On the 26 January 2023, a free to attend, 'improving snake venom research: a community discussion' meeting was held virtually. This webinar brought together researchers from around the world to discuss current neutralisation of venom lethality mouse assays that are used globally to assess the efficacy of therapies for snakebite envenoming. The assay's strengths and weaknesses were highlighted, and we discussed what improvements could be made to refine and reduce animal testing, whilst supporting preclinical antivenom and drug discovery for snakebite envenoming. This report summarises the issues highlighted, the discussions held, with additional commentary on key perspectives provided by the authors.
Topics: Antivenins; Animals; Snake Venoms; Mice; Snake Bites; Humans
PubMed: 38708289
DOI: 10.12688/f1000research.148223.1 -
Toxins Dec 2023In North Africa, scorpion stings pose an urgent public health problem, particularly for children with high morbidity and mortality rates. The main species implicated are...
In North Africa, scorpion stings pose an urgent public health problem, particularly for children with high morbidity and mortality rates. The main species implicated are the (), (), and (). Immunotherapy is the specific therapeutic approach aimed at directly neutralizing toxins, despite their severity and rapid diffusion. In the present study, we evaluate, histologically and immunohistologically, the neutralization potency of the selective antivenom produced against, among other species, the , , and at the level of the tissue alterations in Swiss mice, as experimental subjects. Firstly, the lethal doses 50 test was conducted to assess the venom's toxic activity, and then the median effective dose of the antivenom was determined against each venom. The histological and immunohistological analyses were performed by injecting the sublethal dose of venom, the complex venom and antivenom, or the antivenom 2 h following inoculation of venom. Our study revealed the highest toxicity of the , followed by the and then the venom. The neutralizing ability and effectiveness of the antivenom to completely or partially neutralize the tissular damages were demonstrated in all organs studied: brain, heart, lungs, liver, and kidneys. Our results highlighted the important cytoplasmic and membranous staining in the heart compared to the brain tissue for the three scorpion venoms. Therefore, the scorpionic antivenoms are able to reach their target even at the tissue level. Immunotherapy represents the specific and recommended treatment against the scorpionic stings in North Africa.
Topics: Child; Animals; Mice; Humans; Antivenins; Venoms; Scorpions; Africa, Northern; Animals, Poisonous
PubMed: 38251233
DOI: 10.3390/toxins16010016 -
Toxins Jul 2023This study investigated the clinical characteristics, treatments, and outcomes of envenomation involving cobra species in Thailand (, , and ). Data of patients who had...
This study investigated the clinical characteristics, treatments, and outcomes of envenomation involving cobra species in Thailand (, , and ). Data of patients who had been bitten by a cobra or inoculated via the eyes/skin in 2018-2021 were obtained from the Ramathibodi Poison Center. There were 1045 patients admitted during the 4-year study period (bite, n = 539; ocular/dermal inoculation, n = 506). Almost all patients with ocular/dermal inoculation had eye involvement and ocular injuries, but none had neurological effects. Most of the patients bitten by a cobra had local effects (69.0%) and neurological signs and symptoms (55.7%). The median interval between the bite and the onset of neurological symptoms was 1 h (range, 10 min to 24 h). Accordingly, patients should be observed closely in hospitals for at least 24 h after a bite. Intubation with ventilator support was required in 45.5% of patients and for a median duration of 1.1 days. Antivenom was administered in 63.5% of cases. There were nine deaths, most of which resulted from severe infection. Neurological effects and intubation were significantly more common after a monocled cobra bite than after a spitting cobra bite. The administration of antivenom with good supportive care, including the appropriate management of complications, especially wound infection, might decrease fatality.
Topics: Animals; Elapidae; Antivenins; Elapid Venoms; Snake Bites; Retrospective Studies; Naja
PubMed: 37505737
DOI: 10.3390/toxins15070468 -
Revista Da Sociedade Brasileira de... 2023Venomous fish are commonly found in Brazilian waters. The most important marine venomous fish species are stingrays (Dasyatidae, Gimnuridae, Myliobatidae, and...
Venomous fish are commonly found in Brazilian waters. The most important marine venomous fish species are stingrays (Dasyatidae, Gimnuridae, Myliobatidae, and Rhinopteridae families), catfish (Ariidae family), scorpionfish and lionfish (both Scorpaenidae family), and toadfish (Batrachoididae family). Meanwhile, Potamotrygonidae stingrays and Pimelodidae catfish are the most important venomous freshwater fish. The mechanisms of envenomation vary and involve various venomous apparatuses and glands. Despite not being highly developed, these venomous apparatuses in fish appear rudimentary, using structures such as fins and rays to inoculate toxins and rarely presenting with specialized structures. Toxins are produced by glandular tissue made up of proteinaceous cells, lacking true glands, and are positioned along the inoculation structures. However, systemic manifestations are rare. No antivenom serum has been developed for any species of American venomous fish. Brazilian venomous fish and their venoms have only recently attracted attention, leading to new studies not only addressing clinical issues in humans, but also exploring the discovery of new active substances with immense pharmacological potential.
Topics: Humans; Animals; Fish Venoms; Brazil; Bites and Stings; Antivenins; Catfishes
PubMed: 37531519
DOI: 10.1590/0037-8682-0144-2023 -
Biochimie Jan 2024In Colombia, the Micrurus genus comprises 30 species, including M. mipartitus and M. dumerilii, which are of major clinical relevance due to their wide geographical...
In Colombia, the Micrurus genus comprises 30 species, including M. mipartitus and M. dumerilii, which are of major clinical relevance due to their wide geographical distribution and the number of snakebites inflicted by them. These neurotoxic envenomations are characterized by neuromuscular paralysis attributed to venom components such as three-finger toxins (3FTx) and phospholipases (PLA). Additionally, there is limited information available on the neutralizing coverage of commercially available antivenoms, underscoring the need to perform studies to assess the cross-neutralizing ability of these life-saving products. Therefore, we present an in-depth immunorecognition analysis by the anticoral-INS antivenom from Colombia on the M. mipartitus and M. dumerilii venoms. The antivenom cross-recognized the whole venoms and their components with different intensities. For instance, the antivenom showed better recognition on PLAs than on 3FTxs in both venoms. Moreover, at doses tested, the antivenom totally neutralized the lethal effect of M. dumerilii venom; however, it did not neutralize this effect induced by M. mipartitus venom and its main toxic components from the southwestern region of the department of Antioquia. Furthermore, the anticoral-INS antivenom displayed better cross-immunorecognition of PLA-predominant Micrurus venoms than of 3FTx-predominant Micrurus venoms. This highlights the need to include venoms from both types of venom patterns in the immunization mixture to produce antivenoms against coral snakes. Finally, our results suggest the need for further research to optimize the composition of immunizing mixtures for antivenom production and improve their efficacy against coral snake envenomation in Colombia and the Americas.
Topics: Animals; Antivenins; Coral Snakes; Elapid Venoms; Phospholipases A2; Elapidae
PubMed: 37844754
DOI: 10.1016/j.biochi.2023.10.009 -
Trends in Immunology Apr 2024Snakebite envenomings kill ~100 000 victims each year and leave many more with permanent sequelae. Antivenoms have been available for more than 125 years but are in need...
Snakebite envenomings kill ~100 000 victims each year and leave many more with permanent sequelae. Antivenoms have been available for more than 125 years but are in need of innovation. A new study by Khalek et al. highlights broadly neutralizing human monoclonal antibodies (mAbs) that might be used to develop recombinant antivenoms with superior therapeutic benefits.
Topics: Humans; Animals; Antivenins; Snake Bites; Antibodies, Monoclonal; Snakes
PubMed: 38538486
DOI: 10.1016/j.it.2024.03.001 -
Toxicon : Official Journal of the... May 2024African spitting cobra, Naja nigricincta nigricincta (Zebra snake), envenomation is an important cause of snakebite morbidity and mortality in Namibia. The snake is...
Naja nigricincta nigricincta venom, a murine model. Evaluation of skeletal and cardio-myonecrosis, kidney injury and inflammatory response along with neutralisation efficacy by the SAIMR/SAVP - And EchiTAb-Plus-ICP polyvalent antivenoms.
African spitting cobra, Naja nigricincta nigricincta (Zebra snake), envenomation is an important cause of snakebite morbidity and mortality in Namibia. The snake is endemic to central and northern Namibia as well as southern Angola. The venom is mainly cytotoxic, resulting in aggressive dermo-necrosis and often accompanied by severe systemic complications. No specific antivenom exists. Rhabdomyolysis, systemic inflammatory response, haemostatic abnormalities, infective necrotising fasciitis as well as acute kidney failure have been documented. Based on murine models, this study assessed SAVP/SAIMR - and EchiTAb-Plus-ICP polyvalent antivenom neutralisation as well as subdermal necrosis. Additional muscle, cardiac, kidney and lung histology, creatine kinase measurements and post-mortems were performed. An intravenous median lethal dose (LD50) of Naja nigricincta nigricincta venom was determined at 18.4 (CI: 16.3; 20.52) μg and a subdermal lethal dose at 15.3(CI: 12.96; 17.74)μg. The SAIMR/SAVP polyvalent antivenom median effective dose (ED50) was 1.2 ml antivenom/1 mg venom equating to a potency (WHO) of 1 ml antivenom neutralising 0.63 mg venom and approximately 240 ml (24 vials) needed for initial treatment. The ED50 of the EchiTAb-Plus-ICP was 1 ml antivenom/1 mg venom and a potency of 65 mg venom/ml antivenom (3.3 x LD), estimating 230 ml (23 vials) for treatment. Histology and serology (creatine kinase) evidenced venom induced skeletal myotoxicity, which was not prevented by the antivenoms tested. Cardiac myonecrosis, an inflammatory response, direct venom kidney tubular necrosis and cardio-pulmonary failure were documented.
Topics: Animals; Antivenins; Mice; Elapid Venoms; Snake Bites; Necrosis; Disease Models, Animal; Muscle, Skeletal; Inflammation; Lethal Dose 50; Naja; Male; Creatine Kinase; Kidney
PubMed: 38631492
DOI: 10.1016/j.toxicon.2024.107719 -
Toxins Oct 2023venoms are rich in enzymes acting on platelets and coagulation. This action is dependent on two major co-factors, i.e., calcium and phospholipids, while antivenoms...
venoms are rich in enzymes acting on platelets and coagulation. This action is dependent on two major co-factors, i.e., calcium and phospholipids, while antivenoms variably neutralize venom-related coagulopathy effects. Our aims were (i) to describe the composition of and venoms; (ii) to study their activity on the whole blood using rotational thromboelastometry (ROTEM); (iii) to evaluate the contribution of calcium and phospholipids in their activity; and (iv) to compare the effectiveness of four antivenoms (Bothrofav, Inoserp South America, Antivipmyn TRI, and PoliVal-ICP) on the procoagulant activity of these two venoms. Venom composition was comparable. Both venoms exhibited hypercoagulant effects. venom was completely dependent on calcium but less dependent on phospholipids than venom to induce in vitro coagulation. The four antivenoms neutralized the procoagulant activity of the two venoms; however, with quantitative differences. Bothrofav was more effective against both venoms than the three other antivenoms. The relatively similar venom-induced effects in vitro were unexpected considering the opposite clinical manifestations resulting from envenomation (i.e., systemic bleeding with and thrombosis with ). In vivo studies are warranted to better understand the pathophysiology of systemic bleeding and thrombosis associated with bites.
Topics: Animals; Antivenins; Bothrops; Calcium; Hemorrhage; Crotalid Venoms; Thrombosis; Snake Bites
PubMed: 37888645
DOI: 10.3390/toxins15100614 -
BMC Public Health Jun 2024To analyze the vulnerability factors of snakebite patients in China.
OBJECTIVE
To analyze the vulnerability factors of snakebite patients in China.
METHODS
Multi-stage random sampling was used as the main sampling method and snowball sampling as the auxiliary sampling method. The knowledge, attitude and behavior of snakebite among Chinese residents were investigated. Non-parametric test was used to compare the percentage differences in residents' knowledge, attitude and behavior of snakebite, and generalized linear regression analysis was used to analyze the influencing factors, and the vulnerability factors of snakebite patients were comprehensively analyzed.
RESULTS
A total of 6338 subjects were included in this study, of which 68.4% were males, and 58.6% were farmers, workers and service personnel. The median total score of knowledge, attitude, and behavior was 26 (22,36). The patients who were improperly treated after injury were ligation proximal to the affected area (23.43%), squeezing (21.82%), and oral and suction wounds (8.74%). Did not go to hospital due to poverty (1351 cases) and did not receive antivenom (2068 cases). There were 21.32% and 32.63%, respectively. Among 4270 patients injected with antivenom 30.7% were vaccinated within 2 h. Among the patients who went to the hospital for treatment (4987), 75.0% arrived at the hospital within 6 h; Among the 4,761 patients who made emergency calls, 37.4% were treated within 0.5 h.
CONCLUSIONS
Snakebite patients in China have weak knowledge about snakebite, low awareness of medical treatment, lack of correct prevention and emergency treatment measures, dependence on folk remedies, poor housing and so on. In addition, there are low availability of antivenoms and unreasonable distribution of medical resources in some areas of China. Multisectoral and multidisciplinary cooperation should be developed to prevent and control snakebites in order to reduce the burden caused by snakebites.
Topics: Snake Bites; Humans; China; Male; Female; Adult; Health Knowledge, Attitudes, Practice; Middle Aged; Young Adult; Adolescent; Antivenins; Risk Factors; Surveys and Questionnaires; Aged
PubMed: 38926898
DOI: 10.1186/s12889-024-19169-3