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M.E. de Almeida Sbrogio

Bio: M.E. de Almeida Sbrogio is an academic researcher. The author has contributed to research in topics: Antivenom & Bothrops. The author has an hindex of 1, co-authored 1 publications receiving 8 citations.


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Journal ArticleDOI
TL;DR: The concept of antivenoms was first developed by Henry Sewall in 1887 when he demonstrated that pigeons could be immunized against the effects of pygmy rattlesnake venom by successive inoculations of increasing doses of venom.
Abstract: The concept of antivenoms was first developed by Henry Sewall in 1887 when he demonstrated that pigeons could be immunized against the effects of pygmy rattlesnake venom by successive inoculations of increasing doses of venom (1). In 1894, Phisalix and Bertrand first used heat-treated venom for immunization, and a year later Albert Calmette showed that serum from inoculated rabbits could protect against the effects of venom when infused into healthy rabbits before venom challenge. In the same year, Calmette used serum from an immunized horse to treat human envenomation following a cobra bite (2), and this was followed by the production of the first specific immune serum against cobra venom by Fraser. The first commercial equine antivenoms were produced by Calmette in 1898 for use in Vietnam, and in 1911, Vital Brazil first carried out large-scale antivenom production in Brazil. Antivenom was subsequently produced in a number of different countries including the United States, Australia, Brazil, and Japan (3,4).

158 citations

Journal ArticleDOI
TL;DR: Fresh frozen plasma appeared to speed the recovery of coagulopathy and should be considered in bleeding patients, and antivenom is the major treatment for VICC, but there is currently little high-quality evidence to support effectiveness.
Abstract: 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.

148 citations

Journal ArticleDOI
TL;DR: The evidence for the efficacy and safety of existing and in-development snake antivenoms, and to list the alternatives to Fav-Afrique in sub-Saharan Africa, are reviewed.
Abstract: Of the 24 neglected tropical diseases (NTDs) and conditions listed by WHO, snakebite is among the top killers [1]. Tens of thousands of people die each year as a result of snakebite envenoming, with close to 50,000 deaths in India alone [2] and up to 32,000 in sub-Saharan Africa [3]. Yet there are few sources of effective, safe, and affordable antivenoms. The regions that bear the highest snakebite burden are especially underserved [4]. The Fav-Afrique antivenom, produced by Sanofi Pasteur (France), is considered safe and effective and is one of the few antivenoms to be approved by a Stringent Regulatory Authority (French National Regulatory Authority), although limited formal evidence has been published [5,6]. It is polyvalent, targeting most of the medically important snake species in sub-Saharan Africa. In particular, it is highly effective in treating envenoming by Echis ocellatus, the West African saw-scaled viper [5–7] that causes great morbidity and mortality throughout the West and Central African savannah. The venom of E. ocellatus may induce systemic haemorrhage, coagulopathy, and shock, as well as extensive local tissue damage. In the absence of treatment, the case fatality rate is 10%–20% [8]. Medecins Sans Frontieres (MSF) uses Fav-Afrique in its projects in sub-Saharan Africa, notably in Paoua in Central African Republic (CAR), where E. ocellatus envenoming is frequent [9]. Worryingly, MSF has been informed that the production of Fav-Afrique by Sanofi Aventis will be permanently discontinued. The last batch was released in January 2014, with an expiry date of June 2016. All the vials produced have already been sold by Sanofi Pasteur. Although several alternative antivenom products target a similar list of species as Fav-Afrique, there is currently no evidence of their safety and effectiveness. We aimed to review the evidence for the efficacy and safety of existing and in-development snake antivenoms, and to list the alternatives to Fav-Afrique in sub-Saharan Africa.

54 citations

Journal ArticleDOI
TL;DR: The inflammatory effects and mechanisms induced by viper snake venoms, particularly from the Bothrops genus, are summarized, which strongly activate platelet functions and highlight selected venom components that both stimulate platelets functions and exhibit pro-inflammatory activities, thus providing insights into the possible role(s) of thromboinflammation in viper envenomation.
Abstract: Envenomation by viperid snakes is characterized by systemic thrombotic syndrome and prominent local inflammation. To date, the mechanisms underlying inflammation and blood coagulation induced by Viperidae venoms have been viewed as distinct processes. However, studies on the mechanisms involved in these processes have revealed several factors and signaling molecules that simultaneously act in both the innate immune and hemostatic systems, suggesting an overlap between both systems during viper envenomation. Moreover, distinct classes of venom toxins involved in these effects have also been identified. However, the interplay between inflammation and hemostatic alterations, referred as to thromboinflammation, has never been addressed in the investigation of viper envenomation. Considering that platelets are important targets of viper snake venoms and are critical for the process of thromboinflammation, in this review, we summarize the inflammatory effects and mechanisms induced by viper snake venoms, particularly from the Bothrops genus, which strongly activate platelet functions and highlight selected venom components (metalloproteases and C-type lectins) that both stimulate platelet functions and exhibit pro-inflammatory activities, thus providing insights into the possible role(s) of thromboinflammation in viper envenomation.

33 citations

Journal ArticleDOI
TL;DR: Although the high initial dose regimen is not more effective than the low initial dose, it offers the practical advantage of being a single dose, while not incurring higher consumption or enhanced risk of adverse reaction.
Abstract: Background Currently, there is inadequate evidence on which to base clinical management of neurotoxic snakebite envenoming, especially in the choice of initial antivenom dosage. This randomised controlled trial compared the effectiveness and safety of high versus low initial antivenom dosage in victims of neurotoxic envenoming. Methodology/ Principal findings This was a balanced, randomised, double-blind trial that was conducted in three health care centers located in the Terai plains of Nepal. Participants received either low (two vials) or high (10 vials) initial dosage of Indian polyvalent antivenom. The primary composite outcome consisted of death, the need for assisted ventilation and worsening/recurrence of neurotoxicity. Hourly evaluations followed antivenom treatment. Between April 2011 and October 2012, 157 snakebite victims were enrolled, of which 154 were analysed (76 in the low and 78 in the high initial dose group). Sixty-seven (43·5%) participants met the primary outcome definition. The proportions were similar in the low (37 or 48.7%) vs. high (30 or 38.5%) initial dose group (difference = 10·2%, 95%CI [-6·7 to 27·1], p = 0·264). The mean number of vials used was similar between treatment groups. Overall, patients bitten by kraits did worse than those bitten by cobras. The occurrence of treatment-related adverse events did not differ among treatment groups. A total of 19 serious adverse events occurred, including seven attributed to antivenom. Conclusions This first robust trial investigating antivenom dosage for neurotoxic snakebite envenoming shows that the antivenom currently used in Nepal performs poorly. Although the high initial dose regimen is not more effective than the low initial dose, it offers the practical advantage of being a single dose, while not incurring higher consumption or enhanced risk of adverse reaction. The development of new and more effective antivenoms that better target the species responsible for bites in the region will help improve future patients’ outcomes. Trial registration The study was registered on clinicaltrials.gov (NCT01284855) (GJ 5/1)

31 citations