Efficacy of Indian polyvalent snake antivenoms against Sri Lankan snake venoms: lethality studies or clinically focussed in vitro studies

Maduwage, Kalana; Silva, Anjana; O’Leary, Margaret A.; Hodgson, Wayne Clarence

doi:10.1038/srep26778

Cited by 65 publications

(63 citation statements)

References 36 publications

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“…At these concentrations antivenom failed to prevent the myotoxic effects of Sri Lankan Russell’s viper venom in-vitro . Although this may be due to the low efficacy of the antivenom against the myotoxins [39], testing higher antivenom concentrations was not possible due to the practical limitations of increasing antivenom concentration in the tissue organ bath environment without affecting the osmolarity of the physiological salt solution. It was therefore not possible to determine the efficacy of the Indian polyvalent antivenom to neutralise the myotoxic effects of Sri Lankan Russell’s viper venom, because such a large amount of venom was required to cause myotoxicity requiring very high concentrations of antivenom.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Pharmacological Investigation of Myotoxicity in Sri Lankan Russell’s Viper (Daboia russelii) Envenoming

et al. 2016

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BackgroundSri Lankan Russell’s viper (Daboia russelii) envenoming is reported to cause myotoxicity and neurotoxicity, which are different to the effects of envenoming by most other populations of Russell’s vipers. This study aimed to investigate evidence of myotoxicity in Russell’s viper envenoming, response to antivenom and the toxins responsible for myotoxicity.Methodology and FindingsClinical features of myotoxicity were assessed in authenticated Russell’s viper bite patients admitted to a Sri Lankan teaching hospital. Toxins were isolated using high-performance liquid chromatography. In-vitro myotoxicity of the venom and toxins was investigated in chick biventer nerve-muscle preparations. Of 245 enrolled patients, 177 (72.2%) had local myalgia and 173 (70.6%) had local muscle tenderness. Generalized myalgia and muscle tenderness were present in 35 (14.2%) and 29 (11.8%) patients, respectively. Thirty-seven patients had high (>300 U/l) serum creatine kinase (CK) concentrations in samples 24h post-bite (median: 666 U/l; maximum: 1066 U/l). Peak venom and 24h CK concentrations were not associated (Spearman’s correlation; p = 0.48). The 24h CK concentrations differed in patients without myotoxicity (median 58 U/l), compared to those with local (137 U/l) and generalised signs/symptoms of myotoxicity (107 U/l; p = 0.049). Venom caused concentration-dependent inhibition of direct twitches in the chick biventer cervicis nerve-muscle preparation, without completely abolishing direct twitches after 3 h even at 80 μg/ml. Indian polyvalent antivenom did not prevent in-vitro myotoxicity at recommended concentrations. Two phospholipase A2 toxins with molecular weights of 13kDa, U1-viperitoxin-Dr1a (19.2% of venom) and U1-viperitoxin-Dr1b (22.7% of venom), concentration dependently inhibited direct twitches in the chick biventer cervicis nerve-muscle preparation. At 3 μM, U1-viperitoxin-Dr1a abolished twitches, while U1-viperitoxin-Dr1b caused 70% inhibition of twitch force after 3h. Removal of both toxins from whole venom resulted in no in-vitro myotoxicity.ConclusionThe study shows that myotoxicity in Sri Lankan Russell’s viper envenoming is mild and non-life threatening, and due to two PLA2 toxins with weak myotoxic properties.

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Section: Discussionmentioning

confidence: 99%

Clinical and Pharmacological Investigation of Myotoxicity in Sri Lankan Russell’s Viper (Daboia russelii) Envenoming

et al. 2016

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“…More recently, the efficacy of seven antivenoms distributed in sub-Saharan Africa has been studied against the venom of Echis ocellatus using neutralization tests and antivenomics [91,93]. Similar assessments have been performed in Asia [138], Australia [139] and Papua New Guinea [79,132]. It is necessary to expand these efforts in order to generate a complete picture of the preclinical spectrum of efficacy of antivenoms in the world.…”

Section: The Need Of International Partnerships To Evaluate Antivmentioning

confidence: 99%

Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead

Gutiérrez

Solano

Plá

et al. 2017

Toxins

132

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Animal-derived antivenoms constitute the mainstay in the therapy of snakebite envenoming. The efficacy of antivenoms to neutralize toxicity of medically-relevant snake venoms has to be demonstrated through meticulous preclinical testing before their introduction into the clinical setting. The gold standard in the preclinical assessment and quality control of antivenoms is the neutralization of venom-induced lethality. In addition, depending on the pathophysiological profile of snake venoms, the neutralization of other toxic activities has to be evaluated, such as hemorrhagic, myotoxic, edema-forming, dermonecrotic, in vitro coagulant, and defibrinogenating effects. There is a need to develop laboratory assays to evaluate neutralization of other relevant venom activities. The concept of the 3Rs (Replacement, Reduction, and Refinement) in Toxinology is of utmost importance, and some advances have been performed in their implementation. A significant leap forward in the study of the immunological reactivity of antivenoms against venoms has been the development of “antivenomics”, which brings the analytical power of mass spectrometry to the evaluation of antivenoms. International partnerships are required to assess the preclinical efficacy of antivenoms against snake venoms in different regions of the world in order to have a detailed knowledge on the neutralizing profile of these immunotherapeutics.

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“…This situation is despite the fact that all institutions had medicines needed for managing anaphylactic shock following anti-venom serum administration. However the efficacy of Indian anti-venom serum (VINS and BHARAT are used in SL) against SL snake venom is questionable [22]. …”

Section: Discussionmentioning

confidence: 99%

Availability of essential medicines in selected public, primary and secondary health care institutions of a rural Sri Lankan district: a spot survey

Rathish

Premarathna

Jayathilake

et al. 2017

BMC Health Serv Res

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BackgroundAssessment of the availability of essential medicines, in rural areas of countries with free state health care system, is scarce. Dependence on essential medicines among the population in rural sector is considered to be high. Assessing the availability of essential medicines in selected state owned primary and secondary health care institutions of a rural district will help to identify areas where improvement is needed.MethodsA descriptive cross sectional study, covering selected five primary and one secondary care institutions of a rural Sri Lankan district, was conducted. The national list of essential medicines, Sri Lanka was used as the check list and the guidelines of the WHO–Health Action International were adapted.ResultsThe secondary care institution recorded an overall availability of 71%, whereas the average overall availability of the primary care institutions was 56%. Central dispensaries recorded the lowest availability. Lack of availability of medicines needed for the management of chronic kidney disease, snake bite and poisoning was noted.ConclusionsAvailability of essential medicines in most of the primary and the secondary care institutions were fairly high. Deficiency in medicines needed for the management of emergencies was noted. A need based annual estimate of medicines based on an essential medicine list is suggested.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-016-1969-2) contains supplementary material, which is available to authorized users.

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Efficacy of Indian polyvalent snake antivenoms against Sri Lankan snake venoms: lethality studies or clinically focussed in vitro studies

Cited by 65 publications

References 36 publications

Clinical and Pharmacological Investigation of Myotoxicity in Sri Lankan Russell’s Viper (Daboia russelii) Envenoming

Clinical and Pharmacological Investigation of Myotoxicity in Sri Lankan Russell’s Viper (Daboia russelii) Envenoming

Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead

Availability of essential medicines in selected public, primary and secondary health care institutions of a rural Sri Lankan district: a spot survey

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