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.

/pdf/snake-envenoming-a-disease-of-poverty-4pf8kb7ly5.pdf

Snake Envenoming: A Disease of Poverty

Snake venoms and coagulopathy.

The processes that drive the evolution of snake venom variability, particularly the role of diet, have been a topic of intense recent research interest. Here, we test whether extensive variation in venom composition in the medically important viper genus Echis is associated with shifts in diet. Examination of stomach and hindgut contents revealed extreme variation between the major clades of Echis in the proportion of arthropod prey consumed. The toxicity (median lethal dose, LD50) of representative Echis venoms to a natural scorpion prey species was found to be strongly associated with the degree of arthropod feeding. Mapping the results onto a novel Echis phylogeny generated from nuclear and mitochondrial sequence data revealed two independent instances of coevolution of venom toxicity and diet. Unlike venom LD50, the speed with which venoms incapacitated and killed scorpions was not associated with the degree of arthropod feeding. The prey-specific venom toxicity of arthropod-feeding Echis may thus be adaptive primarily by reducing venom expenditure. Overall, our results provide strong evidence that variation in snake venom composition results from adaptive evolution driven by natural selection for different diets, and underscores the need for a multi-faceted, integrative approach to the study of the causes of venom evolution.

/pdf/coevolution-of-diet-and-prey-specific-venom-activity-444vt5ks40.pdf

Coevolution of diet and prey-specific venom activity supports the role of selection in snake venom evolution

Venomous snakebite is considered the single most important cause of human injury from venomous animals worldwide. Coagulopathy is one of the commonest important systemic clinical syndromes and can be complicated by serious and life-threatening haemorrhage. Venom-induced consumption coagulopathy (VICC) is the commonest coagulopathy resulting from snakebite and occurs in envenoming by Viperid snakes, certain elapids, including Australian elapids, and a few Colubrid (rear fang) snakes. Procoagulant toxins activate the clotting pathway, causing a broad range of factor deficiencies depending on the particular procoagulant toxin in the snake venom. Diagnosis and monitoring of coagulopathy is problematic, particularly in resource-poor countries where further research is required to develop more reliable, cheap clotting tests. MEDLINE and EMBASE up to September 2013 were searched to identify clinical studies of snake envenoming with VICC. The UniPort database was searched for coagulant snake toxins. Despite preclinical studies demonstrating antivenom binding toxins (efficacy), there was less evidence to support clinical effectiveness of antivenom for VICC. There were no placebo-controlled trials of antivenom for VICC. There were 25 randomised comparative trials of antivenom for VICC, which compared two different antivenoms (ten studies), three different antivenoms (four), two or three different doses or repeat doses of antivenom (five), heparin treatment and antivenom (five), and intravenous immunoglobulin treatment and antivenom (one). There were 13 studies that compared two groups in which there was no randomisation, including studies with historical controls. There have been numerous observational studies of antivenom in VICC but with no comparison group. Most of the controlled trials were small, did not use the same method for assessing coagulopathy, varied the dose of antivenom, and did not provide complete details of the study design (primary outcomes, randomisation, and allocation concealment). Non-randomised trials including comparison groups without antivenom showed that antivenom was effective for some snakes (e.g., Echis), but not others (e.g., Australasian elapids). Antivenom is the major treatment for VICC, but there is currently little high-quality evidence to support effectiveness. Antivenom is not risk free, and adverse reactions can be quite common and potentially severe. Studies of heparin did not demonstrate it improved outcomes in VICC. Fresh frozen plasma appeared to speed the recovery of coagulopathy and should be considered in bleeding patients.

/pdf/current-treatment-for-venom-induced-consumption-coagulopathy-52tzaq1l3l.pdf

Current treatment for venom-induced consumption coagulopathy resulting from snakebite.

https://www.wemjournal.org/article/S1080-6032(07)70195-3/pdf

Snakes of Medical Importance in India: Is the Concept of the “Big 4” Still Relevant and Useful?

The Saw-scaled or Carpet Viper (Echis carinatus) whose range extends from Senegal to Bengal probably bites and kills more people than any other species of snake. One hundred and fifteen patients with poisoning caused by its bite were studied in the savanna region of Nigeria, where victims of this snake may occupy 10 per cent of hospital beds. Patients showing no signs of envenoming were excluded. All patients had local swelling at the site of the bite. Other features included local blistering (13 per cent), local necrosis (11 per cent), incoagulable blood (93 per cent), and spontaneous systemic bleeding (57 per cent). There was evidence of disseminated intravascular coagulation in all cases; fibrinogen was severely depleted, fibrin degradation products were increased (mean 1711 +/- 904 micron per ml), but significant thrombocytopenia (less than 103 000 per mm3) was seen in only ten severe cases. Clotting factors V, VIII, II and XIII were depleted, while X and VII were usually normal. Fibrinolytic activity was rarely increased, so it seems likely that a procoagulant action (direct activation of prothrombin) is principal effect of E. carinatus venom on blood coagulation in man. Development of the haemostatic defect was observed as early as 75 minutes and as late as 27 hours after the bite. Spontaneous haemorrhage is clinically the most important effect of E. carinatus venom, causing the five deaths in this series. The relative importance of procoagulant and haemorrhagic components of the venom in causing haemorrhage is discussed. Complement activation via the classical and alternative pathways may have contributed to vascular damage. Mortality was reduced from the untreated level of between 10 and 20 per cent to 2.8 per cent in a group of 107 patients treated with 10 to 110 ml of specific antivenom. The dose was controlled using a simple clotting test. Blood coagulability was restored in two to 39 (mean 12) hours after the first dose of antivenom. Immediate-type serum reactions were observed in 21 per cent of cases. Additional treatment included blood transfusion for patients in haemorrhagic shock and ealry surgical debridement of necrotic tissue at the site of the bite.

Poisoning by bites of the saw-scaled or carpet viper (Echis carinatus) in Nigeria.

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Poisoning by bites of the saw-scaled or carpet viper (Echis carinatus) in Nigeria.