Correction: Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa.
Ontology highlight
ABSTRACT:
SUBMITTER: Harrison RA
PROVIDER: S-EPMC7458313 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Publications
Correction: Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa.
Harrison Robert A RA Oluoch George O GO Ainsworth Stuart S Alsolaiss Jaffer J Bolton Fiona F Arias Ana-Silvia AS Gutiérrez José-María JM Rowley Paul P Kalya Stephen S Ozwara Hastings H Casewell Nicholas R NR
PLoS neglected tropical diseases 20200831 8
[This corrects the article DOI: 10.1371/journal.pntd.0005969.]. ...[more]
Similar Datasets
Project description:BackgroundAntivenom is the treatment of choice for snakebite, which annually kills an estimated 32,000 people in sub-Saharan Africa and leaves approximately 100,000 survivors with permanent physical disabilities that exert a considerable socioeconomic burden. Over the past two decades, the high costs of the most polyspecifically-effective antivenoms have sequentially reduced demand, commercial manufacturing incentives and production volumes that have combined to create a continent-wide vacuum of effective snakebite therapy. This was quickly filled with new, less expensive antivenoms, many of which are of untested efficacy. Some of these successfully marketed antivenoms for Africa are inappropriately manufactured with venoms from non-African snakes and are dangerously ineffective. The uncertain efficacy of available antivenoms exacerbates the complexity of designing intervention measures to reduce the burden of snakebite in sub-Saharan Africa. The objective of this study was to preclinically determine the ability of antivenoms available in Kenya to neutralise the lethal effects of venoms from the most medically important snakes in East Africa.MethodsWe collected venom samples from the most medically important snakes in East Africa and determined their toxicity in a mouse model. Using a 'gold standard' comparison protocol, we preclinically tested the comparative venom-neutralising efficacy of four antivenoms available in Kenya with two antivenoms of clinically-proven efficacy. To explain the variant efficacies of these antivenoms we tested the IgG-venom binding characteristics of each antivenom using in vitro IgG titre, avidity and venom-protein specificity assays. We also measured the IgG concentration of each antivenom.FindingsNone of the six antivenoms are preclinically effective, at the doses tested, against all of the most medically important snakes of the region. The very limited snake polyspecific efficacy of two locally available antivenoms is of concern. In vitro assays of the abilities of 'test' antivenom IgGs to bind venom proteins were not substantially different from that of the 'gold standard' antivenoms. The least effective antivenoms had the lowest IgG content/vial.ConclusionsManufacture-stated preclinical efficacy statements guide decision making by physicians and antivenom purchasers in sub-Saharan Africa. This is because of the lack of both clinical data on the efficacy of most of the many antivenoms used to treat patients and independent preclinical assessment. Our preclinical efficacy assessment of antivenoms available in Kenya identifies important limitations for two of the most commonly-used antivenoms, and that no antivenom is preclinically effective against all the regionally important snakes. The potential implication to snakebite treatment is of serious concern in Kenya and elsewhere in sub-Saharan Africa, and underscores the dilemma physicians face, the need for clinical data on antivenom efficacy and the medical and societal value of establishing independent preclinical antivenom-efficacy testing facilities throughout the continent.
| S-EPMC5646754 | biostudies-literature
Project description:BACKGROUND:Snakebite in India causes the highest annual rates of death (46,000) and disability (140,000) than any other country. Antivenom is the mainstay treatment of snakebite, whose manufacturing protocols, in essence, have remained unchanged for over a century. In India, a polyvalent antivenom is produced for the treatment of envenomations from the so called 'big four' snakes: the spectacled cobra (Naja naja), common krait (Bungarus caeruleus), Russell's viper (Daboia russelii), and saw-scaled viper (Echis carinatus). In addition to the 'big four', India is abode to many other species of venomous snakes that have the potential to inflict severe clinical or, even, lethal envenomations in their human bite victims. Unfortunately, specific antivenoms are not produced against these species and, instead, the 'big four' antivenom is routinely used for the treatment. METHODS:We characterized the venom compositions, biochemical and pharmacological activities and toxicity profiles (mouse model) of the major neglected yet medically important Indian snakes (E. c. sochureki, B. sindanus, B. fasciatus, and two populations of N. kaouthia) and their closest 'big four' congeners. By performing WHO recommended in vitro and in vivo preclinical assays, we evaluated the efficiencies of the commercially marketed Indian antivenoms in recognizing venoms and neutralizing envenomations by these neglected species. FINDINGS:As a consequence of dissimilar ecologies and diet, the medically important snakes investigated exhibited dramatic inter- and intraspecific differences in their venom profiles. Currently marketed antivenoms were found to exhibit poor dose efficacy and venom recognition potential against the 'neglected many'. Premium Serums antivenom failed to neutralise bites from many of the neglected species and one of the 'big four' snakes (North Indian population of B. caeruleus). CONCLUSIONS:This study unravels disturbing deficiencies in dose efficacy and neutralisation capabilities of the currently marketed Indian antivenoms, and emphasises the pressing need to develop region-specific snakebite therapy for the 'neglected many'.
| S-EPMC6894822 | biostudies-literature
Project description:BackgroundSnakebite in India results in over 58,000 fatalities and a vast number of morbidities annually. The majority of these clinically severe envenomings are attributed to Russell's viper (Daboia russelii), which has a near pan-India distribution. Unfortunately, despite its medical significance, the influence of biogeography on the composition and potency of venom from disparate D. russelii populations, and the repercussions of venom variation on the neutralisation efficacy of marketed Indian antivenoms, remain elusive.MethodsHere, we employ an integrative approach comprising proteomic characterisation, biochemical analyses, pharmacological assessment, and venom toxicity profiling to elucidate the influence of varying ecology and environment on the pan-Indian populations of D. russelii. We then conducted in vitro venom recognition experiments and in vivo neutralisation assays to evaluate the efficacy of the commercial Indian antivenoms against the geographically disparate D. russelii populations.FindingsWe reveal significant intraspecific variation in the composition, biochemical and pharmacological activities and potencies of D. russelii venoms sourced from five distinct biogeographic zones across India. Contrary to our understanding of the consequences of venom variation on the effectiveness of snakebite therapy, commercial antivenom exhibited surprisingly similar neutralisation potencies against the majority of the investigated populations, with the exception of low preclinical efficacy against the semi-arid population from northern India. However, the ability of Indian antivenoms to counter the severe morbid effects of Daboia envenoming remains to be evaluated.ConclusionThe concerning lack of antivenom efficacy against the north Indian population of D. russelii, as well as against two other 'big four' snake species in nearby locations, underscores the pressing need to develop pan-India effective antivenoms with improved efficacy in high snakebite burden locales.
| S-EPMC7993602 | biostudies-literature
Project description:The immunoreactivity of EchiTAb-Plus-ICP, an antivenom developed for the treatment of snakebite envenoming in sub-Saharan Africa, to venoms of seven Echis and Bitis species, was assessed by "antivenomics." This proteomic approach is based on the ability of an antivenom to immunodeplete homologous or heterologous venom proteins. Our results show an extensive cross-reactivity of this antivenom against all Echis and Bitis venoms studied, as revealed by the complete immunodepletion of the majority of venom components, including metalloproteinases, serine proteinases, C-type lectin-like proteins, some phospholipases A(2) and L-amino acid oxidase. However, some phospholipases A(2), disintegrins and proteinase inhibitors were immunodepleted to only a partial extent. These results support the hypothesis that immunizing horses with a mixture of the venoms of Echis ocellatus, Bitis arietans, and Naja nigricollis generates antibodies capable of recognizing the majority of components of medically-relevant homologous and heterologous viperid venoms of the genera Bitis and Echis from sub-Saharan Africa.
| S-EPMC2877433 | biostudies-literature
Project description:Community empowerment and engagement is one of the four strategic aims highlighted in the WHO strategy to prevent and control snakebite envenoming. Inappropriate health-seeking behaviours contribute to adverse outcomes, and community engagement is key in driving behavioural change. WHO has highlighted East Africa as a geographical area of concern for snakebite envenoming. The overall aim of the project is to develop a community engagement toolkit for snakebite envenoming and other NTDs. The objective of this scoping review was to identify current practices in recent community engagement in rural East Africa; the applicability of these results to snakebite envenoming are discussed. PubMed, Web of Science, PsycINFO and Google Scholar were searched from 1 January 2017 to 3 September 2020. Search terms were used to identify publications which related to rural communities and health or disease, for both humans and animals. After reviewing the full papers for all geographical areas, 112 publications were included, 30 of which were conducted in East Africa. Papers included nine different countries and covered a broad range of health topics; notably, water, sanitation and hygiene, nutrition, and maternal and child health. Only one publication considered animal health. The most common form of engagement was in the context of a group meeting, lecture, presentation, discussion or question and answer session (63.3%). A variety of locations within the community were used to engage with people, the most common being an individual's household (23.3%). Communication factors was the key influencer for engagement, both positively and negatively. Key barriers to engagement include local languages and health beliefs, literacy levels, mobile phone ownership and the level of mobile Internet coverage, burden of agricultural work and weather conditions. This study provides an extensive overview of recent public health community engagement in East Africa, which will serve as a useful resource for any group seeking to plan an intervention in remote and rural areas in East Africa. Furthermore, it serves as a guide to help tailor community engagement to snakebite envenoming.
| S-EPMC8334718 | biostudies-literature
Project description:BackgroundDeath adders (Acanthophis spp) are found in Australia, Papua New Guinea and parts of eastern Indonesia. This study aimed to investigate the clinical syndrome of death adder envenoming and response to antivenom treatment.Methodology/principal findingsDefinite death adder bites were recruited from the Australian Snakebite Project (ASP) as defined by expert identification or detection of death adder venom in blood. Clinical effects and laboratory results were collected prospectively, including the time course of neurotoxicity and response to treatment. Enzyme immunoassay was used to measure venom concentrations. Twenty nine patients had definite death adder bites; median age 45 yr (5-74 yr); 25 were male. Envenoming occurred in 14 patients. Two further patients had allergic reactions without envenoming, both snake handlers with previous death adder bites. Of 14 envenomed patients, 12 developed neurotoxicity characterised by ptosis (12), diplopia (9), bulbar weakness (7), intercostal muscle weakness (2) and limb weakness (2). Intubation and mechanical ventilation were required for two patients for 17 and 83 hours. The median time to onset of neurotoxicity was 4 hours (0.5-15.5 hr). One patient bitten by a northern death adder developed myotoxicity and one patient only developed systemic symptoms without neurotoxicity. No patient developed venom induced consumption coagulopathy. Antivenom was administered to 13 patients, all receiving one vial initially. The median time for resolution of neurotoxicity post-antivenom was 21 hours (5-168). The median peak venom concentration in 13 envenomed patients with blood samples was 22 ng/mL (4.4-245 ng/mL). In eight patients where post-antivenom bloods were available, no venom was detected after one vial of antivenom.Conclusions/significanceDeath adder envenoming is characterised by neurotoxicity, which is mild in most cases. One vial of death adder antivenom was sufficient to bind all circulating venom. The persistent neurological effects despite antivenom, suggests that neurotoxicity is not reversed by antivenom.
| S-EPMC3459885 | biostudies-literature
Project description:Snakebite is one of the largest risks from wildlife, however little is known about venomous snake distribution, spatial variation in snakebite risk, potential changes in snakebite risk pattern due to climate change, and vulnerable human population. As a consequence, management and prevention of snakebite is hampered by this lack of information. Here we used habitat suitability modeling for 10 medically important venomous snakes to identify high snakebite risk area under climate change in Iran. We identified areas with high snakebite risk in Iran and showed that snakebite risk will increase in some parts of the country. Our results also revealed that mountainous areas (Zagros, Alborz, Kopet-Dagh mountains) will experience highest changes in species composition. We underline that in order to improve snakebite management, areas which were identified with high snakebite risk in Iran need to be prioritized for the distribution of antivenom medication and awareness rising programs among vulnerable human population.
| S-EPMC10199932 | biostudies-literature
Project description:IntroductionSnakebites are a neglected tropical disease. In many areas, envenoming incidence and antivenom administration rates are unknown. This study compared antivenom (AV) availability to rates of envenoming and recommendations to treat (RTT) in South Africa.MethodsThis retrospective study identified, extracted, and reviewed all cases of envenoming (snake bites and spits) reported to the Poisons Information Helpline of the Western Cape of South Africa (PIHWC) from June 1, 2015 to May 31, 2020 by public hospitals in the Western Cape. A standardized interview was administered to the pharmacies of the 40 hospitals in winter and summer to determine how many vials of monovalent and polyvalent AV they had on hand at the time of the call and their expiration dates. Descriptive analysis was used to compare rates of envenoming and recommendations to treat to antivenom stock in winter and summer and by hospital type and location.ResultsPublic hospitals reported 300 envenomings, 122 from snakes. The PIHWC recommended antivenom administration in 26% of cases (N = 32). All hospital pharmacies queried answered our questions. Our study demonstrates urban district hospitals have higher ratios of AV vials compared to mean annual rates of envenoming and RTT than rural district hospitals at both the winter and summer timepoints.ConclusionThis study evaluates antivenom supply and demand in a province of South Africa. The findings suggest South African urban hospitals have a relative excess of antivenom, and thus more capacity to meet demand, than their rural counterparts. It supports consideration of a redistribution of antivenom supply chains to match seasonal and local rates of envenoming. It indicates a need for higher quality, prospective data characterizing envenoming incidence and treatment.
| S-EPMC10517267 | biostudies-literature
Project description:Diagnosing and treating acute severe and recurrent antivenom-related anaphylaxis (ARA) is challenging and reported experience is limited. Herein, we describe our experience of severe ARA in patients with neurotoxic snakebite envenoming in Nepal. Patients were enrolled in a randomised, double-blind trial of high vs. low dose antivenom, given by intravenous (IV) push, followed by infusion. Training in ARA management emphasised stopping antivenom and giving intramuscular (IM) adrenaline, IV hydrocortisone, and IV chlorphenamine at the first sign/s of ARA. Later, IV adrenaline infusion (IVAI) was introduced for patients with antecedent ARA requiring additional antivenom infusions. Preantivenom subcutaneous adrenaline (SCAd) was introduced in the second study year (2012). Of 155 envenomed patients who received ≥ 1 antivenom dose, 13 (8.4%), three children (aged 5-11 years) and 10 adults (18-52 years), developed clinical features consistent with severe ARA, including six with overlapping signs of severe envenoming. Four and nine patients received low and high dose antivenom, respectively, and six had received SCAd. Principal signs of severe ARA were dyspnoea alone (n=5 patients), dyspnoea with wheezing (n=3), hypotension (n=3), shock (n=3), restlessness (n=3), respiratory/cardiorespiratory arrest (n=7), and early (n=1) and late laryngeal oedema (n=1); rash was associated with severe ARA in 10 patients. Four patients were given IVAI. Of the 8 (5.1%) deaths, three occurred in transit to hospital. Severe ARA was common and recurrent and had overlapping signs with severe neurotoxic envenoming. Optimising the management of ARA at different healthy system levels needs more research. This trial is registered with NCT01284855.
| S-EPMC6530221 | biostudies-literature
Project description: Not available
| S-EPMC2573912 | biostudies-literature