We report a comparative venomic and antivenomic characterization of the venoms of newborn and adult specimens of the Central American rattlesnake, Crotalus simus, and of the subspecies cumanensis, durissus, ruruima, and terrificus of South American Crotalus durissus. Neonate and adult C. simus share about 50% of their venom proteome. The venom proteome of 6-week-old C. simus is predominantly made of the neurotoxic heterodimeric phospholipase A(2) (PLA(2) crotoxin) (55.9%) and serine proteinases (36%), whereas snake venom Zn(2+)-metalloproteinases (SVMPs), exclusively of class PIII, represent only 2% of the total venom proteins. In marked contrast, venom from adult C. simus comprises toxins from 7 protein families. A large proportion (71.7%) of these toxins are SVMPs, two-thirds of which belong to the PIII class. These toxin profiles correlate well with the overall biochemical and pharmacological features of venoms from adult (hemorrhagic) and newborn (neurotoxic) C. simus specimens. The venoms of the South American Crotalus subspecies belong to one of two distinct phenotypes. C. d. cumanensis exhibits high levels of SVMPs and low lethal potency (LD(50)), whereas C. d. subspecies terrificus, ruruima, and durissus have low SVMP activity and high neurotoxicity to mice. Their overall toxin compositions explain the outcome of envenomation by these species. Further, in all C. simus and C. durissus venoms, the concentration of neurotoxins (crotoxin and crotamine) is directly related with lethal activity, whereas lethality and metalloproteinase activity show an inverse relationship. The similar venom toxin profiles of newborn C. simus and adult C. durissus terrificus, ruruima, and durissus subspecies strongly suggests that the South American taxa have retained juvenile venom characteristics in the adult form (paedomorphism) along their North-South stepping-stone dispersal. The driving force behind paedomorphism is often competition or predation pressure. The increased concentration of the neurotoxins crotoxin and crotamine in South American rattlesnake venoms strongly argues that the gain of neurotoxicity and lethal venom activities to mammals may have represented the key axis along which overall venom toxicity has evolved during Crotalus durissus invasion of South America. The paedomorphic trend is supported by a decreasing LNC (lethal neurotoxicity coefficient, defined as the ratio between the average LD(50) of the venom and the crotoxin + crotamine concentration) along the North-South axis, coincident with the evolutionary dispersal pattern of the Neotropical rattlesnakes. The indistinguisable immunoreactivity patterns of Costa Rican and Venezuelan polyvalent antivenoms toward C. simus and C. durissus venoms strongly suggest the possibility of using these antivenoms indistinctly for the management of snakebites by adult C. simus and by certain C. d. cumanensis populations exhibiting a hemorrhagic venom phenotype. The antivenomic results also explain why the antivenoms effectively neutralize the hemorrhagic activity of...

The Amazon region reports the highest incidence of snakebite envenomings in Brazil. We aimed to describe the epidemiology of snakebites in the state of Amazonas and to investigate factors associated with disease severity and lethality. We used a nested case-control study, in order to identify factors associated with snakebite severity and mortality using official Brazilian reporting systems, from 2007 to 2012. Patients evolving to severity or death were considered cases and those with non-severe bites were included in the control group. During the study period, 9,191 snakebites were recorded, resulting in an incidence rate of 52.8 cases per 100,000 person/years. Snakebites mostly occurred in males (79.0%) and in rural areas (70.2%). The most affected age group was between 16 and 45 years old (54.6%). Fifty five percent of the snakebites were related to work activities. Age ≤15 years [OR=1.26 (95% CI=1.03-1.52); (p=0.018)], age ≥65 years [OR=1.53 (95% CI=1.09-2.13); (p=0.012)], work related bites [OR=1.39 (95% CI=1.17-1.63); (p<0.001)] and time to medical assistance >6 hours [OR=1.73 (95% CI=1.45-2.07); (p<0.001)] were independently associated with the risk of severity. Age ≥65 years [OR=3.19 (95% CI=1.40-7.25); (p=0.006)] and time to medical assistance >6 hours [OR=2.01 (95% CI=1.15-3.50); (p=0.013)] were independently associated with the risk of death. Snakebites represent an occupational health problem for rural populations in the Brazilian Amazon with a wide distribution. These results highlight the need for public health strategies aiming to reduce occupational injuries. Most cases of severe disease occurred in the extremes of age, in those with delays in medical attention and those caused by Micrurus bites. These features of victims of snakebite demand adequate management according to well-defined protocols, including prompt referral to tertiary centres when necessary, as well as an effective response from surveillance systems and policy makers for these vulnerable groups.

Resumo No Amazonas, o acidente ofídico é um problema de saúde pública pouco conhecido. Por este motivo, foi realizado um estudo descritivo dos acidentes ofídicos atendidos nas Unidades de Saúde de 34 municípios, um distrito e dois pelotões de fronteira do Estado do Amazonas. As características mais comuns encontradas dentre os pacientes foram: agricultor (50,4%), do sexo masculino (81,3%), em idade produtiva (72,1%), picado no membro inferior (88,5%), por jararaca (48,6%) ou surucucu (46,8%), na zona rural de seu município (70,2%) e que só recebeu atendimento médico em tempo superior a seis horas, após acidente (57,3%). As manifestações locais mais freqüentes foram: edema (76,9%), dor (68,7%), eritema (10,2%) e hemorragia (9,3%). Hemorragia (18,8%) foi a manifestação sistêmica mais freqüente. O antiveneno foi administrado em apenas 65,9% dos pacientes. A via mais utilizada foi a endovenosa (52,3%), sendo relevante o uso de vias não mais recomendadas (47,7%). O antiveneno administrado, na maioria dos pacientes, foi o antibotrópico (66,7%). As complicações mais freqüentes foram abcesso (13,7%), necrose (12,3%), infecção secundária (8,3%), insuficiência renal (2,5%) e gangrena (2,5%). Os procedimentos médicos mais usados para o tratamento das complicações foram: drenagem (52,6%), debridamento (28,9%), amputação (10,5%), limpeza cirúrgica (5,3%) e diálise peritoneal (2,6%). A letalidade foi de 1%. Palavras-chaves: Acidente ofídico. Epidemiologia. Clínica. Amazonas. AbstractIn the State of Amazonas, accidents with snakes are a public health problem. For this reasons, the objective of this work was to carry out a descriptive study of the snake accidents attended in the health units of 34 municipalities, one district and two border platoons in the State of Amazonas. The characteristics most commonly observed among those involved in snake accidents were: farmers (50.4%), male (81.3%), belonging to the working age-group (72.1%), bitten on an upper limb (88.5%) by a "jararaca" (48.6%) or a "surucucu" (46.8%) in the rural part of the municipality (70.2%). The local signs and symptoms most frequently observed in those who received medical care more than 6 hours after the accident (57.3%) were edema (76.9%), pain (68.7%), erithema (10.2%) and hemorrhage (9.3%). The systemic manifestation most frequently observed was hemorrhage (18.8%). Serotherapy was administered in only 65.9% of patients, the intravenous route being the route most commonly used to administer the antivenin (52.3%), while other non-recommended routes were widely used. In the majority of patients the antivenin given was antibotropic. The most frequent complications were: abscess 13.7%, necrosis 12.3%, secondary infection 8.3%, renal insufficiency 2.5% and gangrene 2.5%. The medical procedures most used in the treatment of these complications were drainage 52.6%, debridement 28.9%, amputation 10.5%, surgical cleaning 5.3% and peritoneal dialysis 2.6%. The fatality rate was 1%.

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The hypothalamic-pituitary-adrenal and sympathetic-adrenomedullary axes are the main systems activated in response to stress. Alterations in salivary components and flow rate have been associated with oral health problems and psychological stress. Objectives: The aim of the present study was to investigate the influence of psychological stress on salivary flow, total protein concentration and IgG, IgM and IgA concentrations. Methods: Thirty-eight medical students, average age of 21.4 ± 2.1 years and enrolled in the 2nd to 5th years of their course, took part voluntarily in the study which involved two different periods: the first after vacations and the second during the final exams (a gap of 4 months). An Oral Health Questionnaire and the Lipp Inventory of Stress Symptoms for Adults (ISSL) were applied during both these periods. The flow rate, total protein concentration and immunoglobulin titers of saliva samples, collected after stimulation and stored in a container with protease inhibitor, were measured. Results: Analysis of the ISSL showed that 42.1% (n = 16) of the students had stress during the post-vacation period, and 44.7% (n = 17) during the final exams. The students’ salivary flow rate was significantly lower during the latter period than during the post-vacation period (p < 0.0001), regardless of the presence or absence of psychological stress as measured by the ISSL. There was a reduction in salivary flow rate and a consequent reduction in total protein concentration during the exam period (p = 0.0058). However, during both periods of the study there was no significant difference in total salivary protein concentration between the groups of students with or without psychological stress according to the ISSL (p > 0.05). IgG predominated over IgA and IgM (p < 0.001) during both study periods, regardless of the presence or absence of psychological stress. The study period and the presence of stress influenced the secretion of salivary immunoglobulins. IgM titers during the post-vacation period (p = 0.0044), and IgA (p = 0.028), IgG (p = 0.022) and IgM (p = 0.0075) titers during the final exams were higher in students with symptoms of psychological stress. Conclusions: Although the immunoglobulin titers were high, there was a reduction in the students’ salivary flow rates and a consequent reduction in total protein concentrations.

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