Confronting the neglected problem of snake bite envenoming: the need for a global partnership.
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ABSTRACT:
SUBMITTER: Gutierrez JM
PROVIDER: S-EPMC1472552 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMost epidemiological and clinical reports on snake envenoming focus on a single country and describe rural communities as being at greatest risk. Reports linking snakebite vulnerability to socioeconomic status are usually limited to anecdotal statements. The few reports with a global perspective have identified the tropical regions of Asia and Africa as suffering the highest levels of snakebite-induced mortality. Our analysis examined the association between globally available data on snakebite-induced mortality and socioeconomic indicators of poverty.Methodology/principal findingsWe acquired data on (i) the Human Development Index, (ii) the Per Capita Government Expenditure on Health, (iii) the Percentage Labour Force in Agriculture and (iv) Gross Domestic Product Per Capita from publicly available databases on the 138 countries for which snakebite-induced mortality rates have recently been estimated. The socioeconomic datasets were then plotted against the snakebite-induced mortality estimates (where both datasets were available) and the relationship determined. Each analysis illustrated a strong association between snakebite-induced mortality and poverty.Conclusions/significanceThis study, the first of its kind, unequivocally demonstrates that snake envenoming is a disease of the poor. The negative association between snakebite deaths and government expenditure on health confirms that the burden of mortality is highest in those countries least able to deal with the considerable financial cost of snakebite.
| S-EPMC2791200 | biostudies-literature
Project description:Antivenom therapy is currently the standard practice for treating neuromuscular dysfunction in snake envenoming. We reviewed the clinical and experimental evidence-base for the efficacy and effectiveness of antivenom in snakebite neurotoxicity. The main site of snake neurotoxins is the neuromuscular junction, and the majority are either: (1) pre-synaptic neurotoxins irreversibly damaging the presynaptic terminal; or (2) post-synaptic neurotoxins that bind to the nicotinic acetylcholine receptor. Pre-clinical tests of antivenom efficacy for neurotoxicity include rodent lethality tests, which are problematic, and in vitro pharmacological tests such as nerve-muscle preparation studies, that appear to provide more clinically meaningful information. We searched MEDLINE (from 1946) and EMBASE (from 1947) until March 2017 for clinical studies. The search yielded no randomised placebo-controlled trials of antivenom for neuromuscular dysfunction. There were several randomised and non-randomised comparative trials that compared two or more doses of the same or different antivenom, and numerous cohort studies and case reports. The majority of studies available had deficiencies including poor case definition, poor study design, small sample size or no objective measures of paralysis. A number of studies demonstrated the efficacy of antivenom in human envenoming by clearing circulating venom. Studies of snakes with primarily pre-synaptic neurotoxins, such as kraits (Bungarus spp.) and taipans (Oxyuranus spp.) suggest that antivenom does not reverse established neurotoxicity, but early administration may be associated with decreased severity or prevent neurotoxicity. Small studies of snakes with mainly post-synaptic neurotoxins, including some cobra species (Naja spp.), provide preliminary evidence that neurotoxicity may be reversed with antivenom, but placebo controlled studies with objective outcome measures are required to confirm this.
| S-EPMC5408217 | biostudies-literature
Project description:BackgroundSnake bite is a neglected public health problem in the world and one of the major causes of mortality and morbidity in many areas, particularly in the rural tropics. It also poses substantial economic burdens on the snake bite victims due to treatment related expenditure and loss of productivity. An accurate estimate of the risk of snake bite is largely unknown for most countries in the developing world, especially South-East Asia.Methodology/principal findingsWe undertook a national epidemiological survey to determine the annual incidence density of snake bite among the rural Bangladeshi population. Information on frequency of snake bite and individuals' length of stay in selected households over the preceding twelve months was rigorously collected from the respondents through an interviewer administered questionnaire. Point estimates and confidence intervals of the incidence density of snake bite, weighted and adjusted for the multi-stage cluster sampling design, were obtained. Out of 18,857 study participants, over one year a total of 98 snake bites, including one death were reported in rural Bangladesh. The estimated incidence density of snake bite is 623.4/100,000 person years (95% C I 513.4-789.2/100,000 person years). Biting occurs mostly when individuals are at work. The majority of the victims (71%) receive snake bites to their lower extremities. Eighty-six percent of the victims received some form of management within two hours of snake bite, although only three percent of the victims went directly to either a medical doctor or a hospital.Conclusions/significanceIncidence density of snake bite in rural Bangladesh is substantially higher than previously estimated. This is likely due to better ascertainment of the incidence through a population based survey. Poor access to health services increases snake bite related morbidity and mortality; therefore, effective public health actions are warranted.
| S-EPMC2964284 | biostudies-literature
Project description:BackgroundSnakebite is a major public health problem in agricultural communities in the tropics leading to acute local and systemic impairments with resultant disabilities. Snakebite related long-term musculoskeletal disabilities have been a neglected area of research. We conducted a population-based, cross-sectional study in an agricultural community to describe the chronic musculoskeletal disabilities of snake envenoming.Methodology/principal findingsA sample representative of residents of a single district in a region of high incidence of snake envenoming was recruited to identify ever snakebite victims. They were evaluated for chronic musculoskeletal disabilities that had developed immediately or within four weeks after the snakebite and persisted over three months. In-depth interviews, validated musculoskeletal functional assessment criteria and specialists' examinations were utilised. Among the 816 victims, 26 (3.2%, 95% confidence interval: 2.2-4.6%) had musculoskeletal disabilities, persisting on average for 13.4 years (SD = 14.4). The disabilities were mostly in lower limbs (61.5%) and ranged from swelling (34.6%), muscle wasting (46.1%), reduced motion (61.5%), reduced muscle power (50%), impaired balance (26.9%), chronic non-healing ulcers (3.85%), abnormal gait (3.85%), fixed deformities (19.2%) to amputations (15.4%). Based on disability patterns, six snakebite-related musculoskeletal syndromes were recognised. The offending snakes causing disabilities were cobra (30.8%), Russell's viper (26.9%) and hump-nosed viper (7.7%). Cobra bites manifested muscle wasting (87.5%), reduced muscle power (87.5%), joint stiffness (62.5%) and deformities (37.5%) while viper bites manifested impaired balance (42.8%), pain (71.4%) and swelling (71.4%).Conclusions/significanceSnakebite envenoming is associated with considerable long-term musculoskeletal disabilities. Facilities for specialized care and rehabilitation need to be established in high risk areas.
| S-EPMC5096692 | biostudies-literature
Project description:Tuberculosis (TB) is a major threat to global health, recently exacerbated by the emergence of highly drug-resistant forms of the disease-causing pathogen and synergy with HIV/AIDS. In 2006, the Stop TB Partnership published "The global plan to stop TB: 2006--2015," which set out a vision of halving the prevalence of and mortality caused by the disease by 2015, followed by eliminating the disease as a public health problem by 2050. This vision depends on the development of improved diagnostics, simpler treatment, and more effective vaccination. Recently, active translational research pipelines directed toward each of these goals have been established, but improved understanding of the fundamental biology of this complex disease will prove to be the key to radical advances in TB control.
| S-EPMC2276805 | biostudies-other
Project description:Snake envenoming is a serious and neglected public health crisis that is responsible for as many as 125,000 deaths per year, which is one of the reasons the World Health Organization has recently reinstated snakebite envenoming to its list of category A neglected tropical diseases. Here, we investigated the ability of human mast cell proteases to detoxify six venoms from a spectrum of phylogenetically distinct snakes. To this end, we developed a zebrafish model to assess effects on the toxicity of the venoms and characterized the degradation of venom proteins by mass spectrometry. All snake venoms tested were detoxified by degradation of various venom proteins by the mast cell protease tryptase ?, and not by other proteases. Our data show that recombinant human tryptase ? degrades and detoxifies a phylogenetically wide range of venoms, indicating that recombinant human tryptase could possibly be developed as a universal antidote to venomous snakebites.
| S-EPMC6047305 | biostudies-literature
Project description:In the Brazilian Amazon, Bothrops atrox snakebites are frequent, and patients develop tissue damage with blisters sometimes observed in the proximity of the wound. Antivenoms do not seem to impact blister formation, raising questions regarding the mechanisms underlying blister formation. Here, we launched a clinical and laboratory-based study including five patients who followed and were treated by the standard clinical protocols. Blister fluids were collected for proteomic analyses and molecular assessment of the presence of venom and antivenom. Although this was a small patient sample, there appeared to be a correlation between the time of blister appearance (shorter) and the amount of venom present in the serum (higher). Of particular interest was the biochemical identification of both venom and antivenom in all blister fluids. From the proteomic analysis of the blister fluids, all were observed to be a rich source of damage-associated molecular patterns (DAMPs), immunomodulators, and matrix metalloproteinase-9 (MMP-9), suggesting that the mechanisms by which blisters are formed includes the toxins very early in envenomation and continue even after antivenom treatment, due to the pro-inflammatory molecules generated by the toxins in the first moments after envenomings, indicating the need for local treatments with anti-inflammatory drugs plus toxin inhibitors to prevent the severity of the wounds.
| S-EPMC8618272 | biostudies-literature
Project description:BackgroundSnakebite envenoming is a frequently overlooked cause of mortality and morbidity. Data for snake ecology and existing snakebite interventions are scarce, limiting accurate burden estimation initiatives. Low global awareness stunts new interventions, adequate health resources, and available health care. Therefore, we aimed to synthesise currently available data to identify the most vulnerable populations at risk of snakebite, and where additional data to manage this global problem are needed.MethodsWe assembled a list of snake species using WHO guidelines. Where relevant, we obtained expert opinion range (EOR) maps from WHO or the Clinical Toxinology Resources. We also obtained occurrence data for each snake species from a variety of websites, such as VertNet and iNaturalist, using the spocc R package (version 0.7.0). We removed duplicate occurrence data and categorised snakes into three groups: group A (no available EOR map or species occurrence records), group B (EOR map but <5 species occurrence records), and group C (EOR map and ≥5 species occurrence records). For group C species, we did a multivariate environmental similarity analysis using the 2008 WHO EOR maps and newly available evidence. Using these data and the EOR maps, we produced contemporary range maps for medically important venomous snake species at a 5 × 5 km resolution. We subsequently triangulated these data with three health system metrics (antivenom availability, accessibility to urban centres, and the Healthcare Access and Quality [HAQ] Index) to identify the populations most vulnerable to snakebite morbidity and mortality.FindingsWe provide a map showing the ranges of 278 snake species globally. Although about 6·85 billion people worldwide live within range of areas inhabited by snakes, about 146·70 million live within remote areas lacking quality health-care provisioning. Comparing opposite ends of the HAQ Index, 272·91 million individuals (65·25%) of the population within the lowest decile are at risk of exposure to any snake for which no effective therapy exists compared with 519·46 million individuals (27·79%) within the highest HAQ Index decile, showing a disproportionate coverage in reported antivenom availability. Antivenoms were available for 119 (43%) of 278 snake species evaluated by WHO, while globally 750·19 million (10·95%) of those living within snake ranges live more than 1 h from population centres. In total, we identify about 92·66 million people living within these vulnerable geographies, including many sub-Saharan countries, Indonesia, and other parts of southeast Asia.InterpretationIdentifying exact populations vulnerable to the most severe outcomes of snakebite envenoming at a subnational level is important for prioritising new data collection and collation, reinforcing envenoming treatment, existing health-care systems, and deploying currently available and future interventions. These maps can guide future research efforts on snakebite envenoming from both ecological and public health perspectives and better target future estimates of the burden of this neglected tropical disease.FundingBill & Melinda Gates Foundation.
| S-EPMC6115328 | biostudies-literature
Project description:Cellular and inflammatory events were evaluated in mouse muscle after snake venoms Daboia russelii and Bothrops asper injection over time. A murine model of muscle necrosis based on venom injection was used to investigate up to 800 genes involved in fibrosis diseases and tissue regeneration using the multiplex RNA panel Fibrosis V2 from NanoString technology.
2024-03-21 | GSE248215 | GEO
Project description:BackgroundSnake bite is one of the most neglected public health issues in poor rural communities worldwide. In addition to the clinical effects of envenoming, treatment with antivenom frequently causes serious adverse reactions, including hypersensitivity reactions (including anaphylaxis) and pyrogenic reactions. We aimed to investigate the immune responses to Sri Lankan snake envenoming (predominantly by Russell's viper) and antivenom treatment.Methodology/principal findingsPlasma concentrations of Interleukin (IL)-6, IL-10, tumor necrosis factor ? (TNF?), soluble TNF receptor I (sTNFRI), anaphylatoxins (C3a, C4a, C5a; markers of complement activation), mast cell tryptase (MCT), and histamine were measured in 120 Sri Lankan snakebite victims, both before and after treatment with antivenom. Immune mediator concentrations were correlated with envenoming features and the severity of antivenom-induced reactions including anaphylaxis. Envenoming was associated with complement activation and increased cytokine concentrations prior to antivenom administration, which correlated with non-specific systemic symptoms of envenoming but not with coagulopathy or neurotoxicity. Typical hypersensitivity reactions to antivenom occurred in 77/120 patients (64%), satisfying criteria for a diagnosis of anaphylaxis in 57/120 (48%). Pyrogenic reactions were observed in 32/120 patients (27%). All patients had further elevations in cytokine concentrations, but not complement activation, after the administration of antivenom, whether a reaction was noted to occur or not. Patients with anaphylaxis had significantly elevated concentrations of MCT and histamine.Conclusions/significanceWe have demonstrated that Sri Lankan snake envenoming is characterized by significant complement activation and release of inflammatory mediators. Antivenom treatment further enhances the release of inflammatory mediators in all patients, with anaphylactic reactions characterised by high levels of mast cell degranulation but not further complement activation. Anaphylaxis is probably triggered by non allergen-specific activation of mast cells and may be related to the quality of available antivenom preparations, as well as a priming effect from the immune response to the venom itself.
| S-EPMC3723557 | biostudies-literature