Epidemiological study of snakebite cases in Sikkim: Risk modeling with regard to the habitat suitability of common venomous snakes

BackgroundSnakebite envenoming is listed as category ‘A’ Neglected Tropical Disease. To achieve the target of WHO (World Health Organization) 2019, it becomes necessary to understand various attributes associated with snakebite including community awareness, improvisation of medical facilities and to map the potential distribution of venomous snakes responsible for the bite. Hence this study is conducted in Sikkim, India to understand the epidemiology of snakebite in Sikkim. The potential distribution and risk mapping of five common venomous snakes are done for effective management of snakebite cases.Methods and findingsThe snakebite cases registered in six district hospitals and four PHCs (Primary Health Centers) of Sikkim were collected from the year 2011 to 2018. Community survey was also conducted to supplement the data. Ecological Niche Modeling (ENM) was performed to predict the potential habitat of five common venomous snakes of Sikkim. The risk modeling of snakebite cases was done at the level of Gram Panchayat Unit (GPU) using Geographically Weighted Regression (GWR) and Ordinary Linear Square (OLS) model. We found higher number of male victims inflicted with snakebite envenomation. The potential distribution of the five venomous snakes showed satisfactory mean AUC (Area under Curve) value. Both the models showed significant positive association of snakebite cases with habitat suitability of the venomous snakes. Hospital data revealed no death cases whereas community data reported 24 deaths.ConclusionsDeath from snakebite reflected in community data but not in hospital data strongly indicates the people’s belief in traditional medicine. Though people of Sikkim have rich traditional knowledge, in case of snakebite traditional practices may be ineffective leading to loss of life. Sensitizing people and improving medical facilities along with proper transport facilities in rural areas might significantly reduce the snakebite casualties in the state.     

Point-of-care infrared thermal imaging for differentiating venomous snakebites from non-venomous and dry bites

BackgroundLocal envenomation following snakebites is accompanied by thermal changes, which could be visualized using infrared imaging. We explored whether infrared thermal imaging could be used to differentiate venomous snakebites from non-venomous and dry bites.MethodsWe prospectively enrolled adult patients with a history of snakebite in the past 24 hours presenting to the emergency of a teaching hospital in southern India. A standardized clinical evaluation for symptoms and signs of envenomation including 20-minute whole-blood clotting test and prothrombin time was performed to assess envenomation status. Infrared thermal imaging was done at enrolment, 6 hours, and 24 hours later using a smartphone-based device under ambient conditions. Processed infrared thermal images were independently interpreted twice by a reference rater and once by three novice raters.FindingsWe studied 89 patients; 60 (67%) of them were male. Median (IQR) time from bite to enrolment was 11 (6.5–15) hours; 21 (24%) patients were enrolled within 6 hours of snakebite. In all, 48 patients had local envenomation with/without systemic envenomation, and 35 patients were classified as non-venomous/dry bites. Envenomation status was unclear in six patients. At enrolment, area of increased temperature around the bite site (Hot spot) was evident on infrared thermal imaging in 45 of the 48 patients with envenomation, while hot spot was evident in only 6 of the 35 patients without envenomation. Presence of hot spot on baseline infrared thermal images had a sensitivity of 93.7% (95% CI 82.8% to 98.7%) and a specificity of 82.9% (66.3% to 93.4%) to differentiate envenomed patients from those without envenomation. Interrater agreement for identifying hot spots was more than substantial (Kappa statistic >0.85), and intrarater agreement was almost perfect (Kappa = 0.93). Paradoxical thermal changes were observed in 14 patients.ConclusionsPoint-of-care infrared thermal imaging could be useful in the early identification of non-venomous and dry snakebites.     

Health and economic burden estimates of snakebite management upon health facilities in three regions of southern Burkina Faso

BackgroundSnakebite has become better recognized as a significant cause of death and disability in Sub-Saharan Africa, but the health economic consequences to victims and health infrastructures serving them remain poorly understood. This information gap is important as it provides an evidence-base guiding national and international health policy decision making on the most cost-effective interventions to better manage snakebite. Here, we assessed hospital-based data to estimate the health economic burden of snakebite in three regions of Burkina Faso (Centre-Ouest, Hauts Bassins and Sud-Ouest).MethodologyPrimary data of snakebite victims admitted to regional and district health facilities (eg, number of admissions, mortality, hospital bed days occupied) was collected in three regions over 17 months in 2013/14. The health burden of snakebite was assessed using Disability-Adjusted Life Years (DALYs) calculations based upon hospitalisation, mortality and disability data from admitted patients amongst other inputs from secondary sources (eg, populations, life-expectancy and age-weighting constants). An activity-based costing approach to determine the direct cost of snake envenoming included unit costs of clinical staff wages, antivenom, supportive care and equipment extracted from context-relevant literature.FindingsThe 10,165 snakebite victims admitted to hospital occupied 28,164 hospital bed days over 17 months. The annual rate of hospitalisation and mortality of admitted snakebite victims was 173 and 1.39/100,000 population, respectively. The estimated annual (i) DALYs lost was 2,153 (0.52/1,000) and (ii) cost to hospitals was USD 506,413 (USD 49/hospitalisation) in these three regions of Burkina Faso. These costs appeared to be influenced by the number of patients receiving antivenom (10.90% in total) in each area (highest in Sud-Ouest) and the type of health facility.ConclusionThe economic burden of snake envenoming is primarily shouldered by the rural health centres closest to snakebite victims–facilities that are typically least well equipped or resourced to manage this burden. Our study highlights the need for more research in other regions/countries to demonstrate the burden of snakebite and the socioeconomic benefits of its management. This evidence can guide the most cost-effective intervention from government and development partners to meet the snakebite-management needs of rural communities and their health centres.     

Coral snake mimicry: live snakes not avoided by a mammalian predator

The occurrence of coral snake coloration among unrelated venomous and non-venomous New World snake species has often been explained in terms of warning coloration and mimicry. The idea that snake predators would avoid coral snakes in nature seems widely established and is postulated in many discussions on coral snake mimicry. However, the few workers that have tested a potential aposematic function of the conspicuous colour pattern focused exclusively on behaviour of snake predators towards coloured abstract models. Here we report on behaviour of temporarily caged, wild coatis (Nasua narica) when confronted with co-occurring live snakes, among which were two species of venomous coral snakes. Five different types of responses have been observed, ranging from avoidance to predation, yet none of the coatis avoided either of the two coral snake species or other species resembling these. As in earlier studies coatis appeared to avoid coral snake models, our findings show that results from studies with abstract snake models cannot unconditionally serve as evidence for an aposematic function of coral snake coloration.     

Novel transdisciplinary methodology for cross-sectional analysis of snakebite epidemiology at national scale

BackgroundWorldwide, it is estimated that snakes bite 4.5–5.4 million people annually, 2.7 million of which are envenomed, and 81,000–138,000 die. The World Health Organization reported these estimates and recognized the scarcity of large-scale, community-based, epidemiological data. In this context, we developed the “Snake-Byte” project that aims at (i) quantifying and mapping the impact of snakebite on human and animal health, and on livelihoods, (ii) developing predictive models for medical, ecological and economic indicators, and (iii) analyzing geographic accessibility to healthcare. This paper exclusively describes the methodology we developed to collect large-scale primary data on snakebite in humans and animals in two hyper-endemic countries, Cameroon and Nepal.Methodology/Principal findingsWe compared available methods on snakebite epidemiology and on multi-cluster survey development. Then, in line with those findings, we developed an original study methodology based on a multi-cluster random survey, enhanced by geospatial, One Health, and health economics components. Using a minimum hypothesized snakebite national incidence of 100/100,000/year and optimizing design effect, confidence level, and non-response margin, we calculated a sample of 61,000 people per country. This represented 11,700 households in Cameroon and 13,800 in Nepal. The random selection with probability proportional to size generated 250 clusters from all Cameroonian regions and all Nepalese Terai districts. Our household selection methodology combined spatial randomization and selection via high-resolution satellite images. After ethical approval in Switerland (CCER), Nepal (BPKIHS), and Cameroon (CNERSH), and informed written consent, our e-questionnaires included geolocated baseline demographic and socio-economic characteristics, snakebite clinical features and outcomes, healthcare expenditure, animal ownership, animal outcomes, snake identification, and service accessibility.Conclusions/SignificanceThis novel transdisciplinary survey methodology was subsequently used to collect countrywide snakebite envenoming data in Nepal and Cameroon. District-level incidence data should help health authorities to channel antivenom and healthcare allocation. This methodology, or parts thereof, could be easily adapted to other countries and to other Neglected Tropical Diseases.     

Clinical outcomes and outcome measurement tools reported in randomised controlled trials of treatment for snakebite envenoming: A systematic review

BackgroundSnakebite is a priority neglected tropical disease and causes a range of complications that vary depending on the snake species. Randomised clinical trials have used varied outcome measures that do not allow results to be compared or combined. In accordance with the Core Outcomes Measurements in Effectiveness Trials (COMET) initiative, this systematic review aims to support the development of a globally relevant core outcome set for snakebite.MethodsAll randomised controlled trials, secondary analyses of randomised controlled trials and study protocols investigating the efficacy of therapeutics for human snakebite envenoming were eligible for inclusion. Study screening and data extraction were conducted in duplicate by two independent reviewers. All primary and secondary outcome measures were extracted and compiled, as were adverse event outcome measures. Similar outcome measures were grouped into domains. The study was prospectively registered with PROSPERO: CRD42020196160.ResultsThis systematic review included 43 randomised controlled trials, two secondary analyses and 13 study protocols. A total of 382 outcome measures were extracted and, after duplicates were merged, there were 153 unique outcomes. The most frequently used outcome domain (‘venom antigenaemia’) was included in less than one third of the studies. The unique outcomes were classified into 60 outcome domains. Patient-centred outcomes were used in only three of the studies.DiscussionSignificant heterogeneity in outcome measures exists in snakebite clinical trials. Consensus is needed to select outcome measures that are valid, reliable, patient-centred and feasible. The results of this systematic review strongly support the development of a core outcome set for use in snakebite clinical trials.     

What the snake leaves in its wake: Functional limitations and disabilities among snakebite victims in Ghanaian communities

BackgroundThe estimated five million snakebites per year are an important health problem that mainly affect rural poor populations. The global goal is to halve both mortality and morbidity from this neglected tropical disease by 2030. Data on snakebite morbidity are sparse and mainly obtained from hospital records.MethodsThis community-based study was conducted among 379 rural residents with or without a history of snakebite in the Ashanti and Upper West regions of Ghana. All participants in the snakebite group were bitten at least six months before the day of survey. The World Health Organisation Disability Assessment Schedule 2.0 (WHODAS 2.0) and the Buruli Ulcer Functional Limitation Score were used to obtain patient-reported measure of functioning and disability. Long-term consequences were evaluated based on the severity of the symptoms at the time of the snakebite.FindingsThe median (IQR) time since the snakebite was 8.0 (3.5–16.5) years. The relative risk of disability was 1.54 (95% CI, 1.17–2.03) in the snakebite group compared to the community controls. Among patients with clinical symptoms suggesting envenoming at the time of bite, 35% had mild/moderate disabilities compared to 20% in the control group. The disability domains mainly affected by snakebite envenoming were cognition level, mobility, life activities and participation in society. A combination of the severity of symptoms at the time of the bite, age, gender and region of residence most accurately predicted the odds of having functional limitations and disabilities.ConclusionThe burden of snakebite in the community includes long-term disabilities of mild to moderate severity, which need to be considered when designing appropriate public health interventions. Estimating the total burden of snakebite is complicated by geographic differences in types of snakes and their clinical manifestations.     

Mapping snakebite epidemiology in Nicaragua--pitfalls and possible solutions

Background

Snakebites are a public health problem in Nicaragua: it is a tropical developing country, venomous snakes are present and there are reports of snakebites treated both in the formal and informal health care system. We aimed to produce an incidence map using data reported by the health care system that would be used to allocate resources. However, this map may suffer from case detection bias and decisions based on this map will neglect snakebite victims who do not receive healthcare. To avoid this error, we try to identify where underreporting is likely based on available information.

Method and Findings

The Nicaraguan municipalities are categorized by precipitation, altitude and geographical location into regions of assumed homogenous snake prevalence. Socio-economic and healthcare variables hypothesized to be related to underreporting of snakebites are aggregated into an index. The environmental region variable, the underreporting index and three demographic variables (rurality, sex and age distribution) are entered in a Poisson regression model of municipality-level snakebite incidence. In this model, the underreporting index is non-linearly associated with snakebite incidence, a finding we attribute to underreporting in the most deprived municipalities. The municipalities with the worst scoring on the underreporting index and those with combined low reported incidence and large rural population are identified as likely underreporting. 3,286 snakebite cases were reported in 2005–2009, corresponding to a 5-year incidence of 56 bites per 100,000 inhabitants (municipality range: 0–600 cases per 100,000 inhabitants).

Conclusions

Using publicly available data, we identified areas likely to be underreporting snakebites and highlighted these areas instead of leaving them “white” on the incidence map. The effects of the case detection bias on the distribution of resources against snakebites could decrease. Although not yet verified empirically, our study provides an example of how snake bite epidemiology may be investigated in similar settings worldwide at a low cost.     

Snake Bite in South Asia: A Review

Snake bite is one of the most neglected public health issues in poor rural communities living in the tropics. Because of serious misreporting, the true worldwide burden of snake bite is not known. South Asia is the world''s most heavily affected region, due to its high population density, widespread agricultural activities, numerous venomous snake species and lack of functional snake bite control programs. Despite increasing knowledge of snake venoms'' composition and mode of action, good understanding of clinical features of envenoming and sufficient production of antivenom by Indian manufacturers, snake bite management remains unsatisfactory in this region. Field diagnostic tests for snake species identification do not exist and treatment mainly relies on the administration of antivenoms that do not cover all of the important venomous snakes of the region. Care-givers need better training and supervision, and national guidelines should be fed by evidence-based data generated by well-designed research studies. Poorly informed rural populations often apply inappropriate first-aid measures and vital time is lost before the victim is transported to a treatment centre, where cost of treatment can constitute an additional hurdle. The deficiency of snake bite management in South Asia is multi-causal and requires joint collaborative efforts from researchers, antivenom manufacturers, policy makers, public health authorities and international funders.     

Integrating human behavior and snake ecology with agent-based models to predict snakebite in high risk landscapes

Snakebite causes more than 1.8 million envenoming cases annually and is a major cause of death in the tropics especially for poor farmers. While both social and ecological factors influence the chance encounter between snakes and people, the spatio-temporal processes underlying snakebites remain poorly explored. Previous research has focused on statistical correlates between snakebites and ecological, sociological, or environmental factors, but the human and snake behavioral patterns that drive the spatio-temporal process have not yet been integrated into a single model. Here we use a bottom-up simulation approach using agent-based modelling (ABM) parameterized with datasets from Sri Lanka, a snakebite hotspot, to characterise the mechanisms of snakebite and identify risk factors. Spatio-temporal dynamics of snakebite risks are examined through the model incorporating six snake species and three farmer types (rice, tea, and rubber). We find that snakebites are mainly climatically driven, but the risks also depend on farmer types due to working schedules as well as species present in landscapes. Snake species are differentiated by both distribution and by habitat preference, and farmers are differentiated by working patterns that are climatically driven, and the combination of these factors leads to unique encounter rates for different landcover types as well as locations. Validation using epidemiological studies demonstrated that our model can explain observed patterns, including temporal patterns of snakebite incidence, and relative contribution of bites by each snake species. Our predictions can be used to generate hypotheses and inform future studies and decision makers. Additionally, our model is transferable to other locations with high snakebite burden as well.     

Declining snake population—why and how: a case study in the Mangrove Swamps of Sundarban, India

Species diversity of reptiles is much higher in Sundarban than in other mangrove ecosystems in India. Presently snakes are declining in Sundarban due to habitat loss caused by tremendous population pressure. Besides, irresponsible killing to avoid snakebite both from poisonous and nonpoisonous varieties is another reason for the gradual declining snake population. According to an intensive household survey in 35 villages in Sundarban, about 22 species (five poisonous and 17 non-poisonous) of snakes have been identified and there appears to have been a general decline in densities. On the contrary, a large number of people are bitten and die from snakebite every year with 0.57 and 0.34 vulnerability and mortality rate per 10,000 people, respectively. The two most commonly observed poisonous species are the common krait, Bungarus caeruleus (51 %) and common cobra, Naja naja (40 %), and that of non-poisonous varieties are the Ptyas mucosus (41 %), Typhlina bramina (34 %), Xenochrophis piscator (12 %), and Amphiesma stolata (10 %). Apart from killing of snakes out of fear; habitat loss, unscientific handling of snakes by snake catchers and charmers, and netting by fisherman contributes to snake mortality to a large extent; 72 % killed snakes are of poisonous varieties, 60 % of which are B. caeruleus, the most venomous snake in Sundarban. This paper is an attempt to highlight some of the important conservation efforts like the introduction of snake firms, alternative employment channels for the snake charmers and catchers, and mass awareness campaign through panchayet (village level governing body) and local NGOs.     

Snakebites in Two Rural Districts in Lao PDR: Community-Based Surveys Disclose High Incidence of an Invisible Public Health Problem

BackgroundThe Lao PDR (Laos) is one of the least developed countries in Asia with an estimated 25% of the population living in poverty. It is the habitat of some highly venomous snakes and the majority of the population earns their living from agricultural activities. Under these circumstances the incidence of snakebites is expected to be high.MethodsTwo cross-sectional, community-based surveys were performed in Champone and Phin district, Savannakhet province, Lao PDR to estimate snakebite incidence. Multistage random sampling was used. In the first stage approximately 40% of all villages in each district were randomly selected. In the second stage 33% of all households in each village were randomly chosen. Members of the selected households were interviewed about snakebites during the previous 12 months.ResultsThirty-five of 9856 interviewees reported a snakebite in a 12 month period in Champone district and 79 of 7150 interviewees in Phin district. The estimated incidence is 355 snakebites per 100,000 persons per year and 1105 per 100,000 in Champone and Phin district respectively. All snakebite victims received treatment by traditional healers or self-treatment at home and nobody went to a hospital. Incidence of snakebites, calculated on the basis of hospital records of 14 district hospitals and Savannakhet provincial hospital, ranged from 3 to 14 cases per 100,000 persons per year between 2012 and 2014.ConclusionIncidence of snakebites is high in rural communities in Laos with significant regional differences. Poverty most likely contributes significantly to the higher number of snakebites in Phin district. Hospital statistics profoundly underestimates snakebite incidence, because the majority of snakebite victims receive only treatment by traditional healers or self-treatment in their village. There is an urgent need to train medical staff and students in management of snakebite patients and make snake antivenom available to cope effectively with this important public health problem in order to prevent fatalities and disabilities.     

Influence of the venom delivery system on intraoral prey transport in snakes

We compared intraoral prey transport in venomous snake species from four families (two atractaspidids, nine elapids, three colubrids, 44 viperids) with that in eight non-venomous colubrid species, most feeding on similar mammalian prey. The morphology of the venom delivery system suggests that intraoral prey transport performance should be slightly decreased in atractaspidids, unmodified in most elapids and venomous colubrids, and increased or unmodified in vipers, as compared to that in non-venomous colubrid snakes. Our measurements of relative intraoral prey transport performance show that differences among families do not match expectations based on morphology or past studies. Decreased performance in Atractaspis results from reduction and loss of teeth on the medial palatal elements and dentaries, but affects only early phases of ingestion. Although joint and bone features of elapids and colubrids are similar, intraoral prey transport performance is significantly lower in elapids than in colubrids. Predicted enhancement of intraoral prey transport performance in vipers as compared to colubrids was not borne out by measurements, presumably because palatopterygoid movement during intraoral prey transport is reduced in many viper species to limit fang erection. Absence of significant performance differences between colubrids and viperids might suggest that evolution of the viperid venom delivery system was subject to little selection pressure from intraoral prey transport. Another possibility is that there are trade-offs between intraoral prey transport and strike performance in vipers related to relative skull mass and jaw fragility. Immobilizing prey prior to intraoral transport places less demand on transport performance in vipers. In this model, the conservative kinesis and greater robustness of the colubrid palate has greater potential for transporting live prey with less risk of injury.     

Knowledge of health workers on snakes and snakebite management and treatment seeking behavior of snakebite victims in Bhutan

BackgroundPublished information on snakebite is rare in Bhutan although remarkably higher number of snakebites and associated deaths are reported from other South Asian countries.Aims and methodologyStructured questionnaire was used to collect knowledge of health workers in snakebite management and health seeking behavior of snakebite victims as observed by health workers. Study was conducted in purposively sampled 10 Dzongkhags (district level administrative units) with higher incidence of snakebites.ResultHeath workers scored 27–91% (with an average of 63%, SD = 14) for 52 questions related to snake identification and snakebite management. Among 118 health workers interviewed, 23% had adequate knowledge on snakes and snakebite management while 77% had inadequate knowledge. Among 32 Doctors, 63% of them scored above or equal to 75%. Health workers from Sarpang scored higher (76%, SD = 11) than those from other Dzongkhags. Snakebite victim''s visit to local (traditional) healers prior to seeking medical help from hospital was observed by 75 (63%) health workers. Fifty one percent of health workers observed patients treated with local methods such as the use of black stone called Jhhar Mauro (believed to absorb snake venom), application of honey, rubbing of green herbal paste made up of Khenpa Shing (Artemisia myriantha Wallich ex Besser var. paleocephala [Pamp] Ling) and consumption of fluid made up of Neem leaf (Azadirachta indica Juss). Use of tight tourniquet as a first aid to snakebite was observed by 80% of the health workers.ConclusionHealth workers lack confidence in snakebite management. Snakebite victims are likely to suffer from harmful local practices and traditional beliefs on local treatment practices. Empowering health workers with adequate knowledge on snakebite management and making locals aware in pre-hospital care of snakebites are needed to improve the pre- and in-hospital management of snakebite in Bhutan.     

A mechanistic model of snakebite as a zoonosis: Envenoming incidence is driven by snake ecology,socioeconomics and its impacts on snakes

Snakebite is the only WHO-listed, not infectious neglected tropical disease (NTD), although its eco-epidemiology is similar to that of zoonotic infections: envenoming occurs after a vertebrate host contacts a human. Accordingly, snakebite risk represents the interaction between snake and human factors, but their quantification has been limited by data availability. Models of infectious disease transmission are instrumental for the mitigation of NTDs and zoonoses. Here, we represented snake-human interactions with disease transmission models to approximate geospatial estimates of snakebite incidence in Sri Lanka, a global hotspot. Snakebites and envenomings are described by the product of snake and human abundance, mirroring directly transmitted zoonoses. We found that human-snake contact rates vary according to land cover (surrogate of occupation and socioeconomic status), the impacts of humans and climate on snake abundance, and by snake species. Our findings show that modelling snakebite as zoonosis provides a mechanistic eco-epidemiological basis to understand snakebites, and the possible implications of global environmental and demographic change for the burden of snakebite.     

The colouration of the venomous coral snakes (family Elapidae) and their mimics (families Aniliidae and Golubridae)

The bright coloured, highly venomous coral snakes, Leptomicrurus, Micrurus and Micruroides (family Elapidae) and a series of harmless or mildly toxic mimics form an important component of the snake fauna of the Americas. Coral snake patterns are defined as any dorsal pattern found in any species of venomous coral snake and/or any dorsal pattern containing a substantial amount of red, pink or orange distributed so as to resemble that of some species of venomous coral snake. The components of coral snake colouration are described and four principal dorsal patterns are recognized: unicolour, bicolour, tricolour and quadricolour. The tricolour patterns may be further clustered based on the number of black bands or rings separating the red ones as: monads, dyads, triads, tetrads or pentads. A detailed classification of all coral snake colour patterns is presented and each pattern is illustrated. The taxonomic distribution of these patterns is surveyed for mimics and the 56 species of highly venomous coral snakes. Among the latter, the most frequent encountered patterns are tricolour monads, tricolour triads and bicolour rings, in that order. No venomous coral snakes have a tricolour dyad, tricolour tetrad or quadricolour pattern. As many as 115 species of harmless or mildly toxic species, c. 18% of all American snakes, are regarded as coral snake mimics. The colouration and behavioural traits of venomous coral snakes combine to form a significant antipredator defence of an aposematic type. The mimics in turn receive protection from predators that innately or through learning avoid coral snake colour patterns. The precise resemblances in colouration between sympatric non-coral snakes and venomous coral snakes and the concordant geographic variation between the two strongly support this view. Batesian mimicry with the highly venomous coral snakes as the models and the other forms as the mimics is the favoured explanation for this situation. It is further concluded that a number of species in the genera Elaphe, Farancia, Nerodia and Thamnophis, although having red in their colouration, should not be included in the coral snake mimic guild.     

Evaluating spatiotemporal dynamics of snakebite in Sri Lanka: Monthly incidence mapping from a national representative survey sample

BackgroundSnakebite incidence shows both spatial and temporal variation. However, no study has evaluated spatiotemporal patterns of snakebites across a country or region in detail. We used a nationally representative population sample to evaluate spatiotemporal patterns of snakebite in Sri Lanka.MethodologyWe conducted a community-based cross-sectional survey representing all nine provinces of Sri Lanka. We interviewed 165 665 people (0.8% of the national population), and snakebite events reported by the respondents were recorded. Sri Lanka is an agricultural country; its central, southern and western parts receive rain mainly from Southwest monsoon (May to September) and northern and eastern parts receive rain mainly from Northeast monsoon (November to February). We developed spatiotemporal models using multivariate Poisson process modelling to explain monthly snakebite and envenoming incidences in the country. These models were developed at the provincial level to explain local spatiotemporal patterns.Principal findingsSnakebites and envenomings showed clear spatiotemporal patterns. Snakebite hotspots were found in North-Central, North-West, South-West and Eastern Sri Lanka. They exhibited biannual seasonal patterns except in South-Western inlands, which showed triannual seasonality. Envenoming hotspots were confined to North-Central, East and South-West parts of the country. Hotspots in North-Central regions showed triannual seasonal patterns and South-West regions had annual patterns. Hotspots remained persistent throughout the year in Eastern regions. The overall monthly snakebite and envenoming incidences in Sri Lanka were 39 (95%CI: 38–40) and 19 (95%CI: 13–30) per 100 000, respectively, translating into 110 000 (95%CI: 107 500–112 500) snakebites and 45 000 (95%CI: 32 000–73 000) envenomings in a calendar year.Conclusions/significanceThis study provides information on community-based monthly incidence of snakebites and envenomings over the whole country. Thus, it provides useful insights into healthcare decision-making, such as, prioritizing locations to establish specialized centres for snakebite management and allocating resources based on risk assessments which take into account both location and season.     

Pathology-specific experimental antivenoms for haemotoxic snakebite: The impact of immunogen diversity on the in vitro cross-reactivity and in vivo neutralisation of geographically diverse snake venoms

BackgroundSnakebite is a neglected tropical disease that causes high global rates of mortality and morbidity. Although snakebite can cause a variety of pathologies in victims, haemotoxic effects are particularly common and are typically characterised by haemorrhage and/or venom-induced consumption coagulopathy. Antivenoms are the mainstay therapeutic for treating the toxic effects of snakebite, but despite saving thousands of lives annually, these therapies are associated with limited cross-snake species efficacy due to venom variation, which ultimately restricts their therapeutic utility to particular geographical regions.Methodology/Principal findingsIn this study we explored the feasibility of generating globally effective pathology-specific antivenoms to counteract the haemotoxic signs of snakebite envenoming. Two different immunogen mixtures, consisting of seven and twelve haemotoxic venoms sourced from geographically diverse and/or medically important snakes, were used to raise ovine polyclonal antibodies, prior to characterisation of their immunological binding characteristics and in vitro neutralisation profiles against each of the venoms. Despite variability of the immunogen mixtures, both experimental antivenoms exhibited broadly comparable in vitro venom binding and neutralisation profiles against the individual venom immunogens in immunological and functional assays. However, in vivo assessments using a murine preclinical model of antivenom efficacy revealed substantial differences in venom neutralisation. The experimental antivenom generated from the seven venom immunogen mixture outperformed the comparator, by providing protective effects against venom lethality caused by seven of the eight geographically diverse venoms tested, including three distinct venoms that were not used as immunogens to generate this antivenom. These findings suggest that a core set of venom immunogens may be sufficient to stimulate antibodies capable of broadly neutralising a geographically diverse array of haemotoxic snake venoms, and that adding additional venom immunogens may impact negatively on the dose efficacy of the resulting antivenom.Conclusions/SignificanceAlthough selection of appropriate immunogens that encapsulate venom toxin diversity without diluting antivenom potency remains challenging and further optimisation is required, the findings from this pilot study suggest that the generation of pathology-specific antivenoms with global utility is likely to feasible, thereby highlighting their promise as future modular treatments for the world’s tropical snakebite victims.     

Snake Envenoming: A Disease of Poverty

Background

Most 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 Findings

We 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/Significance

This 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.