Search

Saw scaled vipers of the genus Echis belong to the family Viperidae and subfamily Viperinae. These vipers are widely distributed from East Africa to Southwest and Central Asia. Echis bite is one of the major causes of mortality in the world. Different populations of these medically important snakes have different venom composition, and the relevant antivenom is highly species-specific. Echis has a complex taxonomic history. For many years, only two species were recognized (i.e., Echis coloratus and E. carinatus). Over the past 50 years, the number of species have been raised to 12, of which six species reside in the Middle East. Phylogenetic studies show that the genus Echis fall into four species groups: the E. carinatus, E. coloratus, E. ocellatus and E. pyramidum groups. Until recently, only E. carinatus in Southwest Asia and India and E. coloratus in Arabia were assigned to the Middle East. Several morphological and phylogenetic studies raised the number of Echis species in the Middle East from two to six. These Middle Eastern vipers belong to three different species groups. An Asian, an Arabian and an African group. Distribution and basal split of the genus Echis, likely have been shaped by vicariance and tectonic events, which have separated or connected the land masses. In this study, a brief review on biogeography, taxonomy and distribution of the genus especially in the Middle East is presented.

Saw scaled vipers of the genus Echis belong to the family Viperidae and subfamily Viperinae. These vipers are widely distributed from East Africa to Southwest and Central Asia. Echis bite is one of the major causes of mortality in the world. Different populations of these medically important snakes have different venom composition, and the relevant antivenom is highly species-specific. Echis has a complex taxonomic history. For many years, only two species were recognized (i.e., Echis coloratus and E. carinatus). Over the past 50 years, the number of species have been raised to 12, of which six species reside in the Middle East. Phylogenetic studies show that the genus Echis fall into four species groups: the E. carinatus, E. coloratus, E. ocellatus and E. pyramidum groups. Until recently, only E. carinatus in Southwest Asia and India and E. coloratus in Arabia were assigned to the Middle East. Several morphological and phylogenetic studies raised the number of Echis species in the Middle East from two to six. These Middle Eastern vipers belong to three different species groups. An Asian, an Arabian and an African group. Distribution and basal split of the genus Echis, likely have been shaped by vicariance and tectonic events, which have separated or connected the land masses. In this study, a brief review on biogeography, taxonomy and distribution of the genus especially in the Middle East is presented. [ABSTRACT FROM AUTHOR]

Abstract Background The government of Ethiopia has envisioned digitalizing primary healthcare units through the electronic community health information system (eCHIS) program as a re-engineering strategy aiming to improve healthcare data quality, use, and service provision. The eCHIS is intended as a community-wide initiative to integrate lower health structure with higher administrative health and service delivery unit with the ultimate goal of improving community health. However, the success or failure of the program depends on the level of identifying enablers and barriers of the implementation. Therefore, this study aimed to explore individual and contextual-level enablers and barriers determining eCHIS implementation. Method We conducted an exploratory study to determine the enablers and barriers to successfully implementing eCHIS in rural Wogera district, northwest Ethiopia. In-depth interviews and key informant interviews were applied at participants from multiple sites. A thematic content analysis was conducted based on the key themes reported. We applied the five components of consolidated framework for implementation research to interpret the findings. Results First, based on the intervention's characteristics, implementers valued the eCHIS program. However, its implementation was impacted by the heavy workload, limited or absent network and electricity. Outer-setting challenges were staff turnover, presence of competing projects, and lack of incentive mechanisms. In terms of the inner setting, lack of institutionalization and ownership were mentioned as barriers to the implementation. Resource allocation, community mobilization, leaders’ engagement, and availability of help desk need emphasis for a better achievement. With regard to characteristics of the individuals, limited digital literacy, older age, lack of peer-to-peer support, and limited self-expectancy posed challenges to the implementation. Finally, the importance of mentoring and engaging community and religious leaders, volunteers, having defined plan and regular meetings were identified elements of the implementation process and need emphasis. Conclusion The findings underlined the potential enablers and barriers of eCHIS program for quality health data generation, use, and service provision and highlighted areas that require emphasis for further scale-up. The success and sustainability of the eCHIS require ongoing government commitment, sufficient resource allocation, institutionalization, capacity building, communication, planning, monitoring, and evaluation.

Background: The government of Ethiopia has envisioned digitalizing primary healthcare units through the electronic community health information system (eCHIS) program as a re-engineering strategy aiming to improve healthcare data quality, use, and service provision. The eCHIS is intended as a community-wide initiative to integrate lower health structure with higher administrative health and service delivery unit with the ultimate goal of improving community health. However, the success or failure of the program depends on the level of identifying enablers and barriers of the implementation. Therefore, this study aimed to explore individual and contextual-level enablers and barriers determining eCHIS implementation. Method: We conducted an exploratory study to determine the enablers and barriers to successfully implementing eCHIS in rural Wogera district, northwest Ethiopia. In-depth interviews and key informant interviews were applied at participants from multiple sites. A thematic content analysis was conducted based on the key themes reported. We applied the five components of consolidated framework for implementation research to interpret the findings. Results: First, based on the intervention's characteristics, implementers valued the eCHIS program. However, its implementation was impacted by the heavy workload, limited or absent network and electricity. Outer-setting challenges were staff turnover, presence of competing projects, and lack of incentive mechanisms. In terms of the inner setting, lack of institutionalization and ownership were mentioned as barriers to the implementation. Resource allocation, community mobilization, leaders' engagement, and availability of help desk need emphasis for a better achievement. With regard to characteristics of the individuals, limited digital literacy, older age, lack of peer-to-peer support, and limited self-expectancy posed challenges to the implementation. Finally, the importance of mentoring and engaging community and religious leaders, volunteers, having defined plan and regular meetings were identified elements of the implementation process and need emphasis. Conclusion: The findings underlined the potential enablers and barriers of eCHIS program for quality health data generation, use, and service provision and highlighted areas that require emphasis for further scale-up. The success and sustainability of the eCHIS require ongoing government commitment, sufficient resource allocation, institutionalization, capacity building, communication, planning, monitoring, and evaluation. [ABSTRACT FROM AUTHOR]

Background: IT has brought remarkable change in bridging the digital gap in resource-constrained regions and advancing the health care system worldwide. Community-based information systems and mobile apps have been extensively developed and deployed to quantify and support health services delivered by community health workers. The success and failure of a digital health information system depends on whether and how it is used. Ethiopia is scaling up its electronic community health information system (eCHIS) to support the work of health extension workers (HEWs). For successful implementation, more evidence was required about the factors that may affect the willingness of HEWs to use the eCHIS., Objective: This study aimed to assess HEWs' intentions to use the eCHIS for health data management and service provision., Methods: A cross-sectional study design was conducted among 456 HEWs in 6 pilot districts of the Central Gondar zone, Northwest Ethiopia. A Unified Theory of Acceptance and Use of Technology model was used to investigate HEWs' intention to use the eCHIS. Data were cleaned, entered into Epi-data (version 4.02; EpiData Association), and exported to SPSS (version 26; IBM Corp) for analysis using the AMOS 23 Structural Equation Model. The statistical significance of dependent and independent variables in the model was reported using a 95% CI with a corresponding P value of <.05., Results: A total of 456 HEWs participated in the study, with a response rate of 99%. The mean age of the study participants was 28 (SD 4.8) years. Our study revealed that about 179 (39.3%; 95% CI 34.7%-43.9%) participants intended to use the eCHIS for community health data generation, use, and service provision. Effort expectancy (β=0.256; P=.007), self-expectancy (β=0.096; P=.04), social influence (β=0.203; P=.02), and hedonic motivation (β=0.217; P=.03) were significantly associated with HEWs' intention to use the eCHIS., Conclusions: HEWs need to be computer literate and understand their role with the eCHIS. Ensuring that the system is easy and enjoyable for them to use is important for implementation and effective health data management., (©Tesfahun Hailemariam, Asmamaw Atnafu, Lemma Gezie, Jens Kaasbøll, Jorn Klein, Binyam Tilahun. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 04.03.2024.)

Background: Platyceps ventromaculatus is a non-front-fanged colubrid snake of unknown medical significance. In this study, we highlight the clinical manifestations and outcomes of P. ventromaculatus bites. We also emphasise the need to create awareness among clinicians and the public for its potential to be confused with serious venomous bites such as Echis carinatus sochureki., Methods: This series is part of an ongoing observational clinical study from our tertiary care hospital in Jodhpur, India on the profile and outcomes of snakebite envenoming. Data was collected after approval from Institute Ethics Committee. The date and time of the bite, geographical location, type of human-snake conflict, time-to-reach a healthcare facility, antivenom used (dose), and outcomes were recorded. We retrospectively examined our clinical data for images suggestive of P. ventromaculatus and present the clinical details of these patients. The photographs were identified utilising taxonomic keys for species identification., Results: A total of four images and three patients with bites due to P. ventromaculatus were identified. The clinical effects included mild local erythema, pain, transient local bleeding, and edema. All bites occurred during daylight hours, 2 during agricultural activities, and one at home. Twenty-minute Whole Blood Clotting Test was persistently prolonged for 12 h after the bite in one patient. All patients were treated symptomatically, observed at the emergency department, and discharged within 24 h. None of the patients received antivenom., Conclusions: To our knowledge, P. ventromaculatus has so far not been reported to result in envenoming or medically significant bites. This study highlights that Platyceps bite can present with clinically significant local and possibly systemic findings that may lead to confusion with saw-scaled viper (Echis) envenoming. Clinicians must receive appropriate training so as to be aware and recognize regional snake species that do not require antivenom so as to avoid unnecessary antivenom administration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Snakebite envenoming (SBE) is a priority Neglected Tropical Disease listed by the World Health Organization. South Asia is heavily affected, and virtually all countries in the region import polyvalent antivenom products from India for clinical use. The imported antivenoms, however, have suboptimal effectiveness due to geographical venom variation. Recently, a domestic bivalent product, named Pakistani Viper Antivenom (PVAV) has been developed specifically for Pakistani vipers, Echis carinatus sochureki and Daboia russelii. As a bivalent viperid antivenom, it is unknown yet if PVAV exhibits higher immunological binding and neutralization activities against viper venoms from distant locales compared with polyvalent antivenoms manufactured in India. This study thus examined the preclinical efficacy of PVAV against venoms of Western Russell's Vipers and Saw-scaled Viper subspecies from selected locales in the Indian subcontinent. PVAV generally outperformed the commonly used VINS polyvalent antivenom (VPAV, manufactured in India) in binding toward venoms, and showed superior or comparable neutralization efficacy against the venom procoagulant and hemorrhagic effects of Saw-scaled Vipers as well as Russell's Vipers from Pakistan and Sri Lanka. Based on normalized potency values, PVAV is far more potent than VPAV in neutralizing the lethality of all viper venoms, except that of the Indian Russell's Viper. The study shows conserved antigenicity of toxins responsible for major toxicity across these viperid venoms, and suggests the feasible production of a viper-specific antivenom with higher potency and broader geographical utility for the region., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Snakebite in India is a severe problem as it causes a mortality rate of 58,000 and a disability rate of 140,000 every year which is the highest among any other country. Antivenom is the primary therapy for snakebite, and its manufacturing techniques have essentially stayed unaltered for over a century. Indian polyvalent antivenom, a scientifically validated medicine for treating the toxic effects of snakebites, is available against the venom of the so-called Big Four snakes namely Spectacled cobra (Naja naja), Saw-scaled viper (Echis carinatus), Russell's viper (Daboia russelli) and the Common krait (Bungarus caeruleus), responsible for majority of the deaths in India. India hosts many other species of snakes, including cobras, kraits, saw-scaled vipers, sea snakes, and pit vipers, responsible for clinically severe envenomation. Neutralization strategy has been applied to access the efficacy of antivenoms, crucial for reducing snake bite deaths and disabilities. This review aims to conduct a systematic review and meta-analysis on the neutralization efficiency of the Polyvalent Antivenom (PAV) and focus on the factors that may contribute to the poor recognition of the antivenom towards the venom toxins. Reports focusing on the investigation of antivenom efficacy were searched and collected from several databases. Preclinical studies that reported the neutralization efficacy of the commercial antivenom against the medically important snakes of India were included. The articles were screened based on the inclusion criteria and 8 studies were shortlisted for meta-analysis. Pooled proportion was calculated for the antivenom efficacy reported by the studies and was found to be statistically significant with a 95% confidence interval. The heterogenicity in the venom toxicity and neutralization potency of the antivenom was evident in the overall estimate (proportion) and individual data. We provide comprehensive evidence on antivenom efficacy against medically important snakes from various parts of India which may aid in identifying the gaps in snake envenomation therapy and the need for novel potentially improved treatment of snakebites., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims and Background: Echis carinatus venom is a toxic substance naturally produced by special glands in this snake species. Alongside various toxic properties, this venom has been used for its therapeutic effects, which are applicable in treating various cancers (liver, breast, etc. )., Objective: Nanotechnology-based drug delivery systems are suitable for protecting Echis carinatus venom against destruction and unwanted absorption. They can manage its controlled transfer and absorption, significantly reducing side effects., Methods: In the present study, chitosan nanoparticles were prepared using the ionotropic gelation method with emulsion cross-linking. The venom's encapsulation efficiency, loading capacity, and release rate were calculated at certain time points. Moreover, the nanoparticles' optimal formulation and cytotoxic effects were determined using the MTT assay., Results: The optimized nanoparticle formulation increases cell death induction in various cancerous cell lines. Moreover, chitosan nanoparticles loaded with Echis carinatus venom had a significant rate of cytotoxicity against cancer cells., Conclusion: It is proposed that this formulation may act as a suitable candidate for more extensive assessments of cancer treatment using nanotechnology-based drug delivery systems., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Snake envenomation results in a range of clinical sequelae, and widely used animal-based conventional antivenoms exhibit several limitations including the adverse immunological effects in human snake bite victims. Therefore, human monoclonal anti-snake venom antibodies or fragments can be an alternate therapy for overcoming the existing limitations. We developed venom-neutralizing humanized scFv antibodies and analyzed biochemical mechanisms associated with the inhibition of toxicity. Tomlinson I and J human scFv antibody libraries were screened against Naja naja and Echis carinatus venoms, and seven unique scFv antibodies were obtained. Further, specific toxins of snake venom interacting with each of these scFvs were identified, and phospholipase A2 (PLA2) was found to be prominently captured by the phage-anchored scFv antibodies. Our study indicated PLA2 to be one of the abundant toxins in Naja naja and Echis carinatus venom samples. The scFvs binding to PLA2 were used to perform in vivo survival assay using the mouse model and in vitro toxin inhibition assays. scFv N194, which binds to acidic PLA2, protected 50% of mice treated with Naja naja venom. Significant prolongation of survival time and 16% survival were observed in Echis carinatus venom-challenged mice treated with scFv E113 and scFv E10, respectively. However, a combination comprised of an equal amount of two scFvs, E113 and E10, both interacting with basic PLA2, exhibited synergistically enhanced survival of 33% in Echis carinatus venom-challenged mice. No such synergistically enhanced survival was observed in the case of combinatorial treatment with anti-Naja naja scFvs, N194, and N248. These scFvs demonstrated partial inhibition of venom-induced myotoxicity, and E113 also inhibited hemolysis by 50%, which corroborates the enhanced survival during combinatorial treatment in Echis carinatus venom-challenged mice., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Three families of venomous snakes exist in Iran including Viperidae, Elapidae, and Hydrophidae. Viperidae family is the only family with a widespread distribution. Saw-scaled vipers are important poisonous snakes in Asia and Africa. This name is given to this snake due to the presence of obliquely keeled and serrated lateral body scales. Distribution of this genera is mostly reported in the central and southern regions of Iran. This genus has four main clades: the Echis carinatus, E. coloratus, E. ocellatus, and E. pyramidum. Design pattern in Echis species plays an important role in camouflage and variety of habitat. In the present report, we investigated a specimen from the eastern region of Iran; we examined 25 specimens of Echis that were collected from the eastern region of our country. Among them, only one specimen with a different pattern was found compared with the other 24 specimens by surveying meristic, mensural, and design pattern characters using valid key identifiers. The similarities between the specific Echis with a different pattern and other 24 specimens were also studied and compared. The results of this investigation clearly showed that although the pattern of the lateral white line and block on dorsal body of the specific Echis snake was different, since the meristic and mensural characters were similar to other Echis snakes it can be concluded that this specimen is not a different species; the difference in these patterns may be due to a minor genetic mutation of that specimen. It is the first case report of Echis carinatus sochureki Stemmler, 1969 from Iran with a different pattern.

The Iranian Echis Carinatus (IEC) venom is an exclusive natural source of bio-substances for a wide range of purposes in the blood coagulation cascade. The present study for the first time was aimed to assess novel pro-coagulant, anti-coagulant and anti-platelet proteins, named EC 1.5 (a) , EC 5.1 (b) and EC 4 (a) from Iranian Echis Carinatus (IEC) venom. These peptides were purified by multi-step chromatography methods. Hematological properties were measured using activated clotting tests, platelet aggregation studies, and hemorrhage assessment. Subsequently, these proteins were identified through both their intact molecular mass and peptide mass fingerprint (PMF) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Multiple sequence alignments were performed by ClustalW, Bioedit software. Molegro Data Modeller (MDM) 3.0 software was used to predict the putative tertiary structure of proteins.EC 1.5 (a) , a single-band protein with a molecular mass of 66 and 55 kDa, was observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a reduced and non-reduced state, respectively. Based on the Mascot results, we considered that EC 1.5 (a) is a metalloproteinase of group ΙΙ which exhibited potent pro-coagulant activity. It is predicted that the EC 1.5 (a) with hemorrhagic activity, potentially is a metalloproteinase/disintegrin region that constitutes the disintegrin-like domains. Our findings demonstrate that the disintegrin domain of EC 1.5 (a) lacks platelet aggregation inhibitory activity. On the contrary, this factor shows the property of a platelet aggregation inducer. Also, the EC 5.1 (b) was observed as a single-band protein with a molecular mass of 7.5 kDa. EC 5.1 (b) showed both anti-coagulant and anti-platelet properties. Additionally, the structure of the EC 5.1 (b) fraction is expected to be similar to that of phospholipase A 2 , while EC 4 (a) structure is potentially very similar to that of Echistatin with 5 kDa molecular mass. We introduce the predicted structure of P-II snake venom metalloproteinase/ disintegrin domains, phospholipase A 2 and Echistatin-like fractions. Further research is therefore needed to determine the complete structure of these novel fractions and elucidate their mechanism of action and future therapeutic applications of cardiovascular and homeostasis disorders., Competing Interests: The authors declare that they have no conflicts of interest to disclose.

Abstract Background The whole blood clotting test (WBCT) is a simple test of coagulation that is often used in the assessment, diagnosis, and therapeutic monitoring of snakebite patients in sub-Saharan Africa. WBCT requires only a clean glass tube and several milliliters of venous blood and is ideal for use in poorly equipped health centers throughout the rural areas where 95% of snakebites occur. However, questions surrounding the accuracy and reliability of the test remain unanswered due to variations in testing conditions and a lack of comparative research with which to validate them. This is the first study to evaluate WBCT results at both 20-min (WBCT20) and 30-min (WBCT30) reading times in the same group of snakebite patients. Methods In order to define the best reading time, the authors compared the results of serial WBCT evaluation at both 20 and 30 min after collection in 23 patients treated for snake envenomation in Bembèrèkè, northern Benin. Results WBCT results were identical at both reading times in patients without coagulopathy or when coagulation was restored permanently following a single dose of antivenom. Out of 17 patients with coagulopathy, 14 showed discrepancies between WBCT20 and WBCT30 results in at least one pair of serial evaluations. These could be completely contradictory results (e.g. normal clot at WBCT20 and no clot at WBCT30) or a marked difference in the quality of the clot (e.g. no clotting activity at WBCT20 and an unstable partial clot at WBCT30). WBCT discrepancies were encountered most frequently in three situations: initial normalization of hemostasis following antivenom therapy, detection of a secondary resumption of coagulopathy, or final restoration of hemostasis after a secondary resumption had occurred. Conclusions This study suggests that the WBCT is robust and that a sequential reading should improve the diagnosis and monitoring of venom-induced coagulopathies. It also indicates the possibility of discrepancies in the sensitivity of WBCT20 and WBCT30 for detecting the resolution or reoccurrence of coagulopathy and identifies how these findings, if confirmed, may be used to increase the efficacy and efficiency of antivenom treatment in the field.

The 12 Arab countries of the Middle East are inhabited by 21 species of terrestrial venomous snakes of varying medical importance. This review considers these species, consisting of 16 viperids, 3 elapids and 2 atractaspidines. Iraq, Jordan, Lebanon, Oman, Saudi Arabia, and Yemen report the largest numbers of snakebites and envenomings. Accessible literature in English and Arabic on venomous snakes and snakebites and available antivenoms is reviewed. Clinical effects include potentially misleading symptoms attributable to anxiety and traditional pre-hospital treatments. • This review is intended to serve public health providers in the Arab countries in the Middle East. • The epidemiology and clinical symptoms as well as treatment with antivenoms is discussed. • Antivenoms used is the Arab countries is revised based on current practices. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Razi Institute is the property of Institut Razi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Portable DNA sequencers such as the Oxford Nanopore MinION device have the potential to be truly disruptive technologies, facilitating new approaches and analyses and, in some cases, taking sequencing out of the lab and into the field. However, the capabilities of these technologies are still being revealed. Here we show that single-molecule cDNA sequencing using the MinION accurately characterises venom toxin-encoding genes in the painted saw-scaled viper, Echis coloratus. We find the raw sequencing error rate to be around 12%, improved to 0–2% with hybrid error correction and 3% with de novo error correction. Our corrected data provides full coding sequences and 5′ and 3′ UTRs for 29 of 33 candidate venom toxins detected, far superior to Illumina data (13/40 complete) and Sanger-based ESTs (15/29). We suggest that, should the current pace of improvement continue, the MinION will become the default approach for cDNA sequencing in a variety of species.

This work provides a graphic description of the time course of hemostasis tests results during spontaneous evolution of Echis envenoming and correction of hemostasis disorders with antivenom therapy. The dynamics of fibrinogenemia (g L−1), prothrombin time (PT, %), activated partial thromboplastin time (aPTT, patient/normal ratio) and platelet count (Giga L−1) were collected from coagulopathic envenomed patients of a 12 years prospective study in Africa. Sixty patients were included. 47 of them (78%) received an antivenom (33 ± 12 ml) and 13 did not. Thirty patients (50%) presented bleeding. Only one patient died. The time for fibrinogen to be more than 1 g L−1 was 181 ± 116 h (7.5 days) in the spontaneous evolution group versus 40 ± 21 h in the antivenom group (p < 0.0001). The times for reaching a PT above 50% were 140 ± 64 min (5.8 days) versus 25 ± 15 h (p < 0.00001) and for reaching an aPTT less than 1.5 times the normal values, 116 ± 76 h (4.7 days) versus 10 ± 9 h respectively (p < 0.0002). Thrombopenia was not a common feature of Echis envenomation. This study is the first one to provide a chart of the evolution of the hemostatic tests during envenomation caused by Echis bites. The plots enable to estimate that, in Echis envenomation, in the absence of antivenom administration, hemostasis remains severely affected until the 8–10th day of evolution. On the contrary, efficient antivenom against African vipers corrects clotting functions within a few hours. [ABSTRACT FROM AUTHOR]

Abstract: Fractionation by reversed-phase HPLC of venom from four species of saw-scaled viper: Echis ocellatus, Echis pyramidum leakeyi, Echis carinatus sochureki, and Echis coloratus led to identification in each sample of an abundant protein with cytotoxic activity against human non-small cell lung adenocarcinoma A549 cells. The active component in each case was identified by MALDI-TOF mass fingerprinting of tryptic digests as [Ser49]phospholipase A2 ([Ser49]PLA2). An isoform of [Ser49]PLA2 containing the single Ala18 → Val substitution and a partially characterized [Asp49]PLA2 were also present in the E. coloratus venom. LC50 values against A549 cells for the purified [Ser49]PLA2 proteins from the four species are in the range 2.9–8.5 μM. This range is not significantly different from the range of LC50 values against human umbilical vein endothelial HUVEC cells (2.5–12.2 μM) indicating that the [Ser49]PLA2 proteins show no differential anti-tumor activity. The LC50 value for [Ser49]PLA2 from E. ocellatus against human erythrocytes is >100 μM and the MIC values against Escherichia coli and Staphylococcus aureus are >100 μM. It is suggested that the [Ser49]PLA2 proteins play a major role in producing local tissue necrosis and hemorrhage at the site of envenomation. [Copyright &y& Elsevier]

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 A 2 s 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., Competing Interests: Conflict of interest There is no conflict of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Abstract: The composition of snake venoms shows a high degree of variation at all taxonomic levels, and natural selection for diet has been implicated as a potential cause. Saw-scaled vipers (Echis) provide a good model for studying this phenomenon. The venoms of arthropod feeding species of Echis are significantly more toxic to natural scorpion prey than those of species which feed predominantly upon vertebrate prey. Although testing venom activity on natural prey is important for our understanding of the evolution of venom, natural prey species are often difficult to obtain in sufficient numbers for toxinological work. In order to test the viability of using cheaper and more easily available model organisms for toxicity assessments in evolutionary research, and the extent to which toxicity of arthropod-eating Echis venoms is increased to arthropods in general or targeted to certain groups, we conducted median lethal dosage (LD50) and time to death trials using the desert locust (Schistocerca gregaria) as a model arthropod, rarely consumed by wild Echis. The venoms of arthropod specialist Echis were found to be significantly more toxic to locusts than the venom of a vertebrate feeding outgroup (Bitis arietans), and one arthropod specialist venom was found to be more toxic than those species which feed upon arthropods infrequently or not at all. The venoms of arthropod specialists were also found to cause death and incapacitation faster than the vertebrate feeding outgroup. Despite some similarity of trends, there are considerable differences between the response of natural prey (scorpions) and a model arthropod (locust) to the venoms of Echis species. This suggests that when possible, natural prey rather than convenient model organisms should be used to gain an understanding of the functional significance of variation in venom composition in snakes. [Copyright &y& Elsevier]

Abstract: We analyze the phylogeny of the medically important and taxonomically unresolved viper genus Echis using four mitochondrial gene fragments. The results show that the populations of the genus fall into four main clades: the Echis carinatus, E. coloratus, E. ocellatus and E. pyramidum groups. The E. pyramidum and E. coloratus groups are sister taxa but the interrelationships of this clade and the E. ocellatus and E. carinatus groups are unresolved. The initial divergence of the genus appears to coincide with the collision between Afro-Arabia and Eurasia, and that between the E. coloratus and E. pyramidum clades appears to be associated with the opening of the Red Sea. Later land connections between Africa and Arabia may have contributed to shaping the distribution of the E. pyramidum complex. The present distribution of E. carinatus may be the result of range expansion from southern India. Taxonomically, our results provide molecular evidence for the validity of Echis omanensis, E. khosatzkii, E. borkini and E. jogeri, for the presence of unsuspected genetic diversity within the E. pyramidum complex in eastern Africa, and for the conspecificity of E. carinatus and E. multisquamatus. The status of E. leucogaster remains to be confirmed. [Copyright &y& Elsevier]

Phylogenetic analysis of 1117 bp of mitochondrial DNA sequences (731 bp of cytochrome b and 386 bp of 16S rRNA) indicate that Echis consists of four main clades: E. ocellatus, and the E. coloratus, E. pyramidum, and E. carinatus groups. In the E. coloratus group, E. coloratus itself shows substantial genetic divergence from E. omanensis, corroborating their separate species status. In the E. pyramidum clade, E. pyramidum from Egypt and E. leucogaster from West Africa are genetically very similar, even though samples are separated by 4000 km. South Arabian populations of the E. pyramidum group are much better differentiated from these and two species may be present, animals from Dhofar, southern Oman probably being referable to E. khosatzkii. In the E. carinatus group, specimens of E. carinatus sochureki and E. multisquamatus are very similar in their DNA. The phylogeny indicates that the split between the main groups of Echis was followed by separation of African and Arabian members of the E. pyramidum group, and of E. coloratus and E. omanensis. The last disjunction probably took place at the lowlands that run southwest of the North Oman mountains, which are likely to have been intermittently covered by marine incursions; they also separate the E. pyramidum and E. carinatus groups and several sister taxa of other reptiles. The E. carinatus group may have spread quite recently from North Oman into its very extensive southwest Asian range, and there appears to have been similar expansion of E. pyramidum (including E. leucogaster) in North Africa. Both these events are likely to be associated with the marked climatic changes of the Pleistocene or late Pliocene. Similar dramatic expansions have also recently occurred in three snake species in Iberia. [ABSTRACT FROM AUTHOR]

Abstract: The immobilisation of prey by snakes is most efficiently achieved by the rapid dissemination of venom from its site of injection into the blood stream. Hyaluronidase is a common component of snake venoms and has been termed the “venom spreading factor”. In the absence of nucleotide or protein sequence data to confirm the functional identity of this venom component, we interrogated a venom gland EST database for the saw-scaled viper, Echis ocellatus (Nigeria), using the gene ontology (GO) term “carbohydrate metabolism”. A single hyalurononglucosaminadase-activity matching sequence (EOC00242) was found and used to design PCR primers to acquire the full-length cDNA sequence. Although very different from the bee venom and mammalian hyaluronidase sequences, the E. ocellatus sequence retained all the catalytic, positional and structural residues that characterise this class of carbohydrate metabolising hydrolases. An extraordinarily high level of sequence identity (>95%) was observed in analogous venom gland cDNA sequences isolated (by PCR) from another saw-scaled viper species, E. pyramidum leakeyi (Kenya), and from the sahara horned viper, Cerastes cerastes cerastes (Egypt) and the puff adder, Bitis arietans (Nigeria). Smaller amplicons, lacking hyaluronidase catalytic residues because of 768 bp or 855 bp central deletions, appear to encode either truncated peptides without hyaluronidase activity, or are non-translated transcripts because they lack consensus translation initiating motifs. [Copyright &y& Elsevier]

Abstract: Envenoming by the West African saw-scaled viper, Echis ocellatus resembles that of most vipers, in that it results in local blistering, necrosis and sometimes life-threatening systemic haemorrhage. While effective against systemic envenoming, current antivenoms have little or no effect against local tissue damage. The major mediators of local venom pathology are the zinc-dependant snake venom metalloproteinases (SVMPs). The high degree of structural and functional homology between SVMPs and their mammalian relatives the matrix metalloproteinases (MMPs) suggests that substrate/inhibitor interactions between these subfamilies are likely to be analogous. In this study, four recently developed MMP inhibitors (MMPIs) (Marimastat, AG-3340, CGS-270 23A and Bay-12 9566) are evaluated in addition to three metal ion chelators (EDTA, TPEN and BAPTA) for their ability to inhibit the haemorrhagic activities of the medically important E. ocellatus venom and one of its haemorrhagic SVMPs, EoVMP2. As expected, the metal ion chelators significantly inhibited the haemorrhagic activities of both whole E. ocellatus venom and EoVMP2, while the synthetic MMPIs show more variation in their efficacies. These variations suggest that individual MMPIs show specificity towards SVMPs and that their application to the neutralization of local haemorrhage may require a synthetic MMPI mixture, ensuring that a close structural component for each SVMP is represented. [Copyright &y& Elsevier]

Abstract: Two metalloproteinases, a 24-kDa P-I EoVMP1 and a 56-kDa P-III EoVMP2, have recently been isolated from the venom of the West African saw-scaled viper Echis ocellatus. We now reveal a new 65-kDa haemorrhagic group P-III metalloproteinase which we have designated EoVMP3. The aim of this study was to determine whether these three snake venom metalloproteinases (SVMPs) affect platelets and blood coagulation. EoVMP1 had no effect on the aggregation of washed human platelets, whereas EoVMP2 inhibited collagen-induced platelet aggregation. In contrast, EoVMP3 did not inhibit the aggregation of platelets by collagen but instead activated platelets in the absence of any additional co-factors. All three SVMPs were capable of activating prothrombin to varying degrees and can therefore be described as procoagulants. EoVMP1, EoVMP2 and EoVMP3 share sequence identity with other members of the reprolysin family, but differ greatly in their effects on some of the components that control haemostasis. [Copyright &y& Elsevier]

Abstract: The antigenic relationship between snake venom metalloproteinases (SVMPs) was analysed using rabbit antisera raised against the native forms of two SVMPs purified from Echis ocellatus venom. Using enzyme-linked immunosorbent assay (ELISA), western blotting and two-dimensional SDS-PAGE, our findings show that antibodies raised against EoVMP1, a non-haemorrhagic class P-I 24kDa SVMP, and EoVMP2, a haemorrhagic class P-III 56kDa SVMP, demonstrate cross-reactivities which relate to the domain hierarchy observed in class P-I to P-III/IV SVMPs. A third 65kDa P-III metalloproteinase (designated EoVMP3) was also isolated from E. ocellatus venom using hydrophobic interaction, size exclusion and anion exchange chromatography. In comparative immunoassays, EoVMP2 and EoVMP3 bound strongly to the commercial monovalent ovine Fab fragment antivenom EchiTAb™ (raised against the same venom), but EoVMP1 showed no cross-reactivity. This could indicate that antivenoms may lack antibodies to potentially important venom components. [Copyright &y& Elsevier]

Currently there is a crisis in the supply of antivenom for treatment of snake bite in sub-Saharan Africa. Commercial pressures have resulted in the reduction or even cessation of production of antivenom by European manufacturers while continued production of antivenom in Africa has been threatened by the privatisation of the only remaining company based in Africa. As a consequence, there has been an increase in snake bite morbidity and mortality in many African countries. Two Latin American antivenom manufacturers have agreed to produce antivenom suitable for Africa, using venoms from the species which are of the greatest medical importance in sub-Saharan Africa. Preclinical in vivo assays of neutralising potency demonstrated that a new Pan African antivenom produced in Colombia compared favourably with the existing commercial monospecific and polyspecific antivenoms. This new antivenom, and a similar product being manufactured in Costa Rica, are now candidates for clinical testing at an appropriate site in Africa. [Copyright &y& Elsevier]

EMS16 is a member of the snake venom-derived C-type lectin family of proteins (CLPs) found in the venom of Echis multisquamatus. It binds to glycoprotein Ia/IIa (integrin α2β1), a major collagen receptor of platelets, acting as a potent antagonist of platelet aggregation and cell migration. Amino acid sequencing and cDNA cloning of EMS16 have revealed that it is composed of an A chain of 134 amino acid residues and a B chain of 128 residues. Crystals of EMS16 belong to space group P212121, with unit-cell parameters a = 46.57, b = 59.93, and c = 115.74 Å, and diffract to a resolution of 1.9 Å. Phase determination is underway by means of molecular replacement with the structure of blood coagulation factor IX-binding protein (IX-bp) from habu snake venom (PDB code 1bj3) as the search model. [ABSTRACT FROM AUTHOR]