Paediatric snakebite envenoming: the world's most neglected 'Neglected Tropical Disease'?

Snakebite disproportionally affects children living in impoverished rural communities. The WHO has recently reinstated snakebites on its list of Neglected Tropical Diseases and launched a comprehensive Strategy for the Prevention and Control of Snakebite Envenoming. In the first of a two paper series, we describe the epidemiology, socioeconomic impact and key prevention strategies. We also explore current challenges and priorities including the production and distribution of safe and effective antivenom.Revisión por pare

Two snakebite antivenoms have potential to reduce Eswatini’s dependency upon a single, increasingly unavailable product: Results of preclinical efficacy testing

Background Snakebite is a major public health concern in Eswatini, where treatment relies upon one antivenom—SAIMR Polyvalent. Although effective in treating snakebite, SAIMR Polyvalent is difficult to source outside its manufacturing country (South Africa) and is dauntingly expensive. We compared the preclinical venom-neutralising efficacy of two alternative antivenoms with that of SAIMR Polyvalent against the lethal and tissue-destructive effects of venoms from five species of medically important snakes using in vivo murine assays. The test antivenoms were ‘Panafrican’ manufactured by Instituto Clodomiro Picado and ‘PANAF’ manufactured by Premium Serums & Vaccines. Principal findings In vivo murine preclinical studies identified both test antivenoms were equally or more effective than SAIMR Polyvalent at neutralising lethal and tissue-destructive effects of Naja mossambica venom. Both test antivenoms were less effective than SAIMR Polyvalent at neutralising the lethal effects of Bitis arietans, Dendroaspis polylepis, Hemachatus haemachatus and Naja annulifera venoms, but similarly effective at neutralising tissue damage induced by B. arietans and H. haemachatus venoms. In vitro immunological assays identified that the titres and toxin-specificities of immunoglobulins (iGs) in the test antivenoms were comparable to that of SAIMR Polyvalent. Plasma clotting disturbances by H. haemachatus and N. mossambica were neutralised by the test antivenoms, whereas SAIMR Polyvalent failed to neutralise this bioactivity of N. mossambica venom. B. arietans SVMP activity was equally reduced by all three antivenoms, and H. haemachatus and N. mossambica PLA2 activities were neutralised by all three antivenoms. Conclusions While both Panafrican and PANAF antivenoms exhibited promising preclinical efficacies, both were less poly-specifically effective than SAIMR Polyvalent in these murine assays. The efficacy of these antivenoms against the lethal and tissue-destructive effects of N. mossambica venom, the most common biting species in Eswatini, identify that Panafrican and PANAF antivenoms offer effective alternatives to SAIMR Polyvalent for the treatment of snakebite in Eswatini, and potentially for neighbouring countries

Investigation of the coagulant effects of Sri Lankan snake venoms and the efficacy of antivenoms

Research Doctorate - Doctor of Philosophy (PhD)Coagulopathy is the commonest systemic effect of snake envenoming. Despite this there is limited information on the severity and time course of venom-induced consumption coagulopathy (VICC) and the effect of antivenom. Evidence of the efficacy and effectiveness of antivenom is vital to continue antivenom treatment for envenoming. There is increasing evidence that early administration of antivenom is essential, but there is a lack of diagnostic tests of envenoming that can be used to decide on antivenom administration. The broad aim of this project was to investigate the procoagulant effects of Sri Lankan snake venoms, and the efficacy and effectiveness of antivenoms against these effects. In addition, the study aimed to explore novel methods of testing for envenoming and for the presence of venom in blood. Snake envenoming cases in Sri Lanka were used with the collection of serial clinical and laboratory data, and blood samples from patients admitted to hospitals in Sri Lanka. Coagulopathy from hump-nosed pit viper and Russell’s viper envenoming was investigated by analyzing citrated samples from envenomed patients. Identification of the snake species was by venom specific sandwich enzyme immunoassay (EIA). Antivenom efficacy was assessed in a series of <i>in-vitro</i> and <i>in-vivo</i> animal studies. Antivenom effectiveness was assessed by undertaking two systematic reviews: Cochrane review of placebo randomized controlled trials and a systematic review of prospective and other controlled trials of antivenom for VICC. The results provide a much better description of VICC using clotting times and factor levels in both hump-nosed pit viper and Russell’s viper envenoming, showing prolonged clotting times and different factor deficiencies. Phospholipase A₂ enzyme levels were investigated as a diagnostic test for snake envenoming and will be key to improving outcomes in snake bite cases as it will allow early identification of envenomed patients so antivenom can be given when it is most effective. The efficacy of two Indian antivenoms was assessed, which showed one to be more efficacious but more importantly explored the difference between lethality studies and clinically focused <i>in vitro</i> studies. Two systematic reviews and antivenom for VICC revealed a lack of placebo controlled randomized trials, but that some comparative clinical trials and observational studies provide information on the effectiveness of antivenom

First Aid and pre-hospital practices in snakebite victims: The persistent use of harmful interventions

First aid intervention and pre-hospital (FAPH) practices are common in patients suffering from snakebite envenomation (SBE). In this study, we have reviewed the literature concerning the use of these practices in various regions of the world in the period 1947-2023 based on published prospective studies. A total of 71 publications fulfilled the inclusion criteria. In terms of the total number of patients in all studies that used each FAPH intervention, the most common practice was the application of tourniquets (45.8%). Other FAPH practices described include cuts/incisions (6.7%), the application of a variety of natural or synthetic substances at the bite site (5.6%), and ingestion of natural, usually herbal, remedies (2.9%). Washing the site of the bite was described in 9.1% of patients. There were other less frequent FAPH practices, including suction, splinting-immobilization, pressure-bandage, ice packs, application of a snake/black stone, and administration of alcoholic beverages. There were differences in the extent of application of FAPH interventions in different continents. Tourniquets were highest (55.7%) in Asia. Topical application of various products was common in South America, while pressure-bandage was only reported in Australia. We did not find any statistically significant variations in the frequency of the most frequent FAPH interventions at three-time intervals (before 2006, between 2006 and 2015, and after 2015). Our findings highlight the use of FAPH interventions in patients suffering SBE, some of which are known to be harmful. It is necessary to study these practices to a higher level of geographic granularity, using community-based surveys. Programs tailored to local contexts should be promoted, aimed at avoiding the use of harmful FAPH practices. It is also necessary to assess the efficacy and safety of some interventions through robust preclinical and clinical studies

Enzyme immunoassays for detection and quantification of venoms of Sri Lankan snakes: Application in the clinical setting.

BackgroundDetection and quantification of snake venom in envenomed patients' blood is important for identifying the species responsible for the bite, determining administration of antivenom, confirming whether sufficient antivenom has been given, detecting recurrence of envenoming, and in forensic investigation. Currently, snake venom detection is not available in clinical practice in Sri Lanka. This study describes the development of enzyme immunoassays (EIA) to differentiate and quantify venoms of Russell's viper (Daboia russelii), saw-scaled viper (Echis carinatus), common cobra (Naja naja), Indian krait (Bungarus caeruleus), and hump-nosed pit viper (Hypnale hypnale) in the blood of envenomed patients in Sri Lanka.Methodology / principal findingsA double sandwich EIA of high analytical sensitivity was developed using biotin-streptavidin amplification for detection of venom antigens. Detection and quantification of D. russelii, N. naja, B. caeruleus, and H. hypnale venoms in samples from envenomed patients was achieved with the assay. Minimum (less than 5%) cross reactivity was observed between species, except in the case of closely related species of the same genus (i.e., Hypnale). Persistence/ recurrence of venom detection following D. russelii envenoming is also reported, as well as detection of venom in samples collected after antivenom administration. The lack of specific antivenom for Hypnale sp envenoming allowed the detection of venom antigen in circulation up to 24 hours post bite.ConclusionThe EIA developed provides a highly sensitive assay to detect and quantify five types of Sri Lankan snake venoms, and should be useful for toxinological research, clinical studies, and forensic diagnosis