The other cases were resolved with double doses (8 vials) and less than 2% needed more doses (12 or 16 vials). are mandatory notification events, allowing the acquisition of an accurate registry of each accident and a fluent communication with the health care services that receive and treat the patients. CIAT professionals follow up the cases and register the antivenom neutralization effectivity as well as possible adverse drug reactions. Figure 1 shows the notification flowchart and the steps that occur when a snake bite accident occurs. The snake antivenom vials are widely spread along health centres in the country and they are distributed exclusively by the Ministry of Health. Underreport is almost not existent because the replacement of the snake antivenom in the treatment health center depends on the case notification. Open in a separate window FIGURE 1 Flowchart of notification steps in a snake bite accident. Bothrops snake venom induces consumption of coagulation factors and important oedema among other effects (Fran?a et al., 2003; Serrano et al., 2014; Mamede et al., 2016). Coagulopathy is the major systemic effect of Bothrops envenoming. Antivenoms have been widely used for more than a century for treating snakebites with big success (Chippaux and Goyffon, 1998; Theakston et al., 2003). Unfortunately, using heterologous serum as antivenom make it possible to generate adverse reactions to varying degrees (Morais and Massaldi, 2009; Len et al., 2013; De Silva et al., 2016; Morais, 2018). These could be divided from a clinical point of view into two types: early and late reactions. Early hypersensitivity reactions to antivenoms are the major adverse effect of antivenom treatment, including life threatening anaphylaxis. They can start a few minutes after injecting the antivenom endovenously, and range from mild effects such as fever and malaise, to the most severe effects, such as severe hypotension and anaphylactic shock. The causes of these reactions are varied and Pexacerfont also depend on the patients susceptibility, but generally are due to: activation of the patients complement system by the serum antibodies, presence of impurities or aggregates, presence of Pexacerfont anti-IgE horse proteins in the patient and currently very infrequently, presence of pyrogens in the antivenom (Morais and Rabbit polyclonal to DCP2 Massaldi, 2009; Len et al., 2013; De Silva et al., 2016; Morais, 2018). All these causes (except pyrogen reaction) lead to the degranulation of mast cells and basophils causing the release of active compounds, including histamine, that determine different actions such as vasodilation, hypotension, and increased vascular permeability. Late adverse reaction is a type III hypersensitivity, also called serum sickness, mediated by antigen-antibody complexes. These complexes lead to complement activation and leukocyte infiltration. Serum sickness occurs from 7?days after the triggering injection, but an accelerated form can occur in subjects who are already sensitized Pexacerfont to antivenom (Morais and Massaldi, 2009; Morais, 2018). Manufacturing protocols and methods of snake antivenoms are different in various regions in the world and the standardization of snake antivenom production remains problematic (WHO, 2010b). They may contain whole immunoglobulins or pepsin or papain digested fragments of immunoglobulins such as F (ab)2 or Fab. Monovalent antivenoms are raised against a single snake species, while polyvalent antivenoms are raised against more than one species. Finally, antivenoms can also be in liquid form or lyophilised (Theakston et al., 2003; WHO, 2010b). Historically, in our country, antivenom was produced in the Institute of Hygiene between 1990 and 2000 and in 2011. Since then, antivenoms were supplied by regional producers such as Institute Malbran, Institute Butantan, Funda??o Ezequiel Dias (FUNED) and Institute Vital Brazil, showing good results of efficacy Pexacerfont and security. All of these antivenoms are polyvalent in liquid form and had a potency above 2, 5?mg/ml for both species. Besides this, all of them are composed by F (ab`)2 fragments and are based in ammonium sulphate precipitation protocols with improvements specific to each producer lab (WHO, 2010b). Historical reports of CIAT show that these antivenoms achieved neutralization of between 70 and 85% of the cases with only a single dose (4.
