In-depth immunorecognition and neutralization analyses of Micrurus mipartitus and M. dumerilii venoms and toxins by a commercial antivenom.

In Colombia, the Micrurus genus comprises 30 species, including M. mipartitus and M. dumerilii, which are of major clinical relevance due to their wide geographical distribution and the number of snakebites inflicted by them. These neurotoxic envenomations are characterized by neuromuscular paralysis attributed to venom components such as three-finger toxins (3FTx) and phospholipases (PLA2). Additionally, there is limited information available on the neutralizing coverage of commercially available antivenoms, underscoring the need to perform studies to assess the cross-neutralizing ability of these life-saving products. Therefore, we present an in-depth immunorecognition analysis by the anticoral-INS antivenom from Colombia on the M. mipartitus and M. dumerilii venoms. The antivenom cross-recognized the whole venoms and their components with different intensities. For instance, the antivenom showed better recognition on PLA2s than on 3FTxs in both venoms. Moreover, at doses tested, the antivenom totally neutralized the lethal effect of M. dumerilii venom; however, it did not neutralize this effect induced by M. mipartitus venom and its main toxic components from the southwestern region of the department of Antioquia. Furthermore, the anticoral-INS antivenom displayed better cross-immunorecognition of PLA2-predominant Micrurus venoms than of 3FTx-predominant Micrurus venoms. This highlights the need to include venoms from both types of venom patterns in the immunization mixture to produce antivenoms against coral snakes. Finally, our results suggest the need for further research to optimize the composition of immunizing mixtures for antivenom production and improve their efficacy against coral snake envenomation in Colombia and the Americas.

Envenomation by Micrurus hemprichii in Brazilian Amazonia: A report of three cases.

Herein, we report three new separate cases of human envenomations by Micrurus hemprichii for the Amazon, which is a biome where envenomations by Micrurus are seldom reported. Two women were bitten after stepping on the snakes and one man was bitten while handling the animal. All cases occurred in the peridomicile, in rural areas. The first case evolved mainly to local symptoms, but the patient was discharged before the identification of the snake and had to be called back for observation before being eventually discharged. In the second case, the patient presented transitory dyspnea and she was discharged after four days in hospital. In the third case, the patient showed only local symptoms, but he was about to receive unnecessary antivenom against coral snakes. Cases like these show the importance of educational problems regarding local venomous snakes in order to avoid bites and to provide the correct hospital treatment. For this, trained professionals in cases involving venomous animals are needed.

Antibodies against a single fraction of Micrurus dumerilii venom neutralize the lethal effect of whole venom.

The coralsnake Micrurus dumerilii (Elapidae) is reported to cause envenomings of medical importance. Previous studies characterized the protein composition of its venom, with phospholipase A2 (PLA2) proteins the most abundant. However, it is unknown which venom components are responsible for its lethal toxicity. Fractionation of M. dumerilii venom from Colombia was carried out using RP-HPLC and each fraction was screened for lethal effect in mice at a dose of 20 µg by intraperitoneal route. Results showed that only one fraction, F9, was lethal. This fraction displayed PLA2 activity, induced indirect hemolysis in vitro, as well as edema and myotoxicity in vivo. SDS-PAGE of unreduced F9 evidenced two bands of 8 and 15 kDa, respectively, consistent with the detection of proteins with masses of 13,217.77 Da, 7144.06 Da, and 7665.55 Da. Tryptic digestion of F9 followed by nESI-MS/MS revealed peptide sequences matching proteins of the three-finger toxin (3FTx) and PLA2 families. Immunization of a rabbit with F9 proteins elicited antibody titers up to 1:10,000 by ELISA. After serum fractionation with caprylic acid, the obtained IgG was able to neutralize the lethal effect of the complete venom of M. dumerilii using a challenge of 2 ×LD50 at the IgG/venom ratio of 50:1 (w/w). In conclusion, present results show that the lethal effect of M. dumerilii venom in mice is mainly driven by one fraction which contains 3FTx and PLA2 proteins. The antibodies produced against this fraction cross-recognized other PLA2s and neutralized the lethal effect of whole M. dumerilii venom, pointing out to the potential usefulness of F9 as a relevant antigen for improving current coral snake antivenoms.

In Vivo Cardiotoxic Potential of Micrurus frontalis Venom.

In the present study, we investigated the cardiotoxic potential of Micrurus frontalis venom. Twelve guinea pigs (Cavia porcellus) were distributed in two groups (n = 6), named control and envenomed. Control groups received 0.2 ml of PBS/BSA, while envenomed group received 0.2 ml of the same solution containing 450 µg/kg of M. frontalis venom. Both were intramuscular injections. Electrocardiography, echocardiogram, blood count, and serum biochemistry were performed before and 2 h after inoculation. Necropsy was performed, and histological and ultrastructural analysis of the heart were conducted. First clinical signs were presented as early as 18 min after venom inoculation. All poisoned animals presented flaccid paralysis of both hind and forelimbs, followed by fasciculations and respiratory arrythmia. However, the animals did not die in the first 2 h of poisoning. ECG of the poisoned animals revealed severe ventricular arrythmias, corroborated by reduction of both ejection and shortening fractions, increase in CK, CK-MB, troponin, cardiomyocyte degeneration, fragmentation and mitochondrial damage. M. frontalis venom causes severe heart damage, eliciting both morphological and arrhythmogenic effects after only 2 h of envenomation.

Intense male-male ritual combat In the Micrurus ibiboboca complex (Elapidae) from Northeastern South America

Snakes engaged in agonistic encounters may employ visual and tactile displays that sometimes culminate in ritual combat. Here, we describe novel male-male ritual combat behaviors in South American coral snakes in the Micrurus ibiboboca complex based on the largest observational dataset of ritual combat for any species of the genus Micrurus. The dataset includes 85 photographs and four videographs from six respective observation records of male snakes. We observed four of these fights during the daytime and two during the night. All observations were random encounters in different natural environments during transitional dry seasons (i.e., early dry season between April and June in the west, and the early wet season between August and September on the east coast). During each respective period, precipitation is < 100 mm and is accompanied with decreasing and increasing temperatures, respectively. The following behaviors were observed: recognition, ascent, and alignment. These were followed by orientation, entwining and twisting, rolling, and hovering; then, oblique display stances and topping (including lyre-shaped positioning and dorsal hyperextension). The topping attempts were from high oblique display positions with one male attempting to force the head of the other down. We also observed snapping, where snake opponents twist the heads of each other creating a quick snap-like sound. We suggest these complex ritual displays communicate dominance between snakes.

First record of snakebites by Micrurus ortoni and Micrurus hemprichii (Serpentes: Elapidae) in Colombia and Perú / Primer registro de accidentes ofídicos por mordedura de Micrurus ortoni y Micrurus hemprichii (Serpentes: Elapidae) en Colombia y Perú

We report two snakebites by Micrurus ortoni in Colombia and one by M. hemprichii in Perú. In two of the cases, we observed mild to moderate motor neurological involvement and in all patients, there was a marked sensory effect with hyperesthesia and hyperalgesia radiating from the bite site to the entire ipsilateral hemibody. The only patient who received antivenom, which did not correspond with the type of envenomation, developed equine serum sickness eight days after its administration. The results of the laboratory tests, including an electromyographic study, the photographic record of the clinical manifestations, and the causative agents are presented and discussed.

Se reportan dos casos de mordedura por serpientes de la especie Micrurus ortoni en Colombia y uno por M. hemprichii en Perú. En dos de los casos se observó afección neurológica motora leve a moderada y, en todos, se presentó un acentuado trastorno sensitivo con hiperestesia e hiperalgesia irradiada desde el sitio de la mordedura hacia todo el hemicuerpo comprometido. El único paciente que recibió antiveneno, el cual no era específico para el tipo de envenenamiento, desarrolló una reacción al suero equino a los ocho días de su aplicación. Se presentan y discuten los resultados de las pruebas de laboratorio, incluido el estudio electromiográfico, así como el registro fotográfico de las manifestaciones clínicas y de los agentes causales.

Primer registro de accidentes ofídicos por mordedura de Micrurus ortoni y Micrurus hemprichii (Serpentes: Elapidae) en Colombia y Perú / First record of snakebites by Micrurus ortoni and Micrurus hemprichii (Serpentes: Elapidae) in Colombia and Perú

Resumen | Se reportan dos casos de mordedura por serpientes de la especie Micrurus ortoni en Colombia y uno por M. hemprichii en Perú. En dos de los casos se observó afección neurológica motora leve a moderada y, en todos, se presentó un acentuado trastorno sensitivo con hiperestesia e hiperalgesia irradiada desde el sitio de la mordedura hacia todo el hemicuerpo comprometido. El único paciente que recibió antiveneno, el cual no era específico para el tipo de envenenamiento, desarrolló una reacción al suero equino a los ocho días de su aplicación. Se presentan y discuten los resultados de las pruebas de laboratorio, incluido el estudio electromiográfico, así como el registro fotográfico de las manifestaciones clínicas y de los agentes causales.

Abstract | We report two snakebites by Micrurus ortoni in Colombia and one by M. hemprichii in Perú. In two of the cases, we observed mild to moderate motor neurological involvement and in all patients, there was a marked sensory effect with hyperesthesia and hyperalgesia radiating from the bite site to the entire ipsilateral hemibody. The only patient who received antivenom, which did not correspond with the type of envenomation, developed equine serum sickness eight days after its administration. The results of the laboratory tests, including an electromyographic study, the photographic record of the clinical manifestations, and the causative agents are presented and discussed.

Cardiotoxic Effects of Micrurus surinamensis (Cuvier, 1817) Snake Venom.

Micrurus surinamensis is a coral snake from the Elapidae family of wide distribution in Amazonia Forest. Its venom contains neurotoxins that induce muscular and respiratory paralysis; however, its cardiovascular action is not yet characterized. The aim of this study was to investigate the cardiotoxic effects caused by M. surinamensis poisoning in rodents. Twelve guinea pigs (Cavia porcellus) were distributed in two groups (n = 6) named as control and envenomed. The control group received 0.2 ml of PBS/BSA via intramuscular injection (IM), while envenomed animals received 0.75 µg of venom per g of body weight, also via IM. Electrocardiographic examination (ECG) and biochemical serum tests were conducted before and 2 h after inoculation. ECG of the envenomed animals revealed severe progressive arrhythmias including atrioventricular block, supraventricular, and ventricular extrasystoles. Serum biochemistry showed significant increase in CK, CK-MB, and LDH enzymes corroborating the skeletal and cardiac muscle damage. Myonecrosis and degeneration were observed in both skeletal and heart muscle; nevertheless, transmission electron microscopy revealed cardiac muscle fibers fragmentation. In conclusion, M. surinamensis venom has a potent cardiotoxic activity eliciting arrhythmogenic effects and heart damage after only 2 h of envenomation.

Assessment of neutralization of Micrurus venoms with a blend of anti-Micrurus tener and anti-ScNtx antibodies.

BACKGROUND: Micrurus venoms contain two main groups of toxic protein components: short-chain α-neurotoxins (SNtx) and phospholipases type A2 (PLA2). In North America, generally, the Micrurus venoms have low abundance of SNtx compared to that of PLA2s; however, both are highly toxic to mammals, and consequently both can play a major role in the envenomation processes. Concerning the commercial horse-derived antivenoms against Micrurus from the North America region, they contain a relatively large amount of antibodies against PLA2s, and a low content of antibodies against short chain α-neurotoxins. This is mainly due to the lower relative abundance of SNtxs, and also to its poor immunogenicity due to their size and nature. Hence, Micrurus antivenoms made in North America usually present low neutralizing capacity towards Micrurus venoms whose lethality depend largely on short chain α-neurotoxins, such as South American Micrurus species. METHODS: Horses were hyperimmunized with either the venom of M. tener (PLA2-predominant) or a recombinant short-chain consensus α-neurotoxin (ScNtx). Then, the combination of the two monospecific horse antibodies (anti-M. tener and anti-ScNtx) was used to test their efficacy against eleven Micrurus venoms. RESULTS: The blend of anti-M. tener and anti-ScNtx antibodies had a better capacity to neutralize the lethality of diverse species from North, Central and South American Micrurus venoms. The antibodies combination neutralized both the ScNtx and ten out of eleven Micrurus venom tested, and particularly, it neutralized the venoms of M. distans and M. laticollaris that were neither neutralized by monospecific anti-M. tener nor anti-ScNtx. CONCLUSIONS: These results provide a proof-of-principle for using recombinant immunogens to enrich poor or even non-neutralizing antisera against elapid venoms containing short chain α-neurotoxins to develop antivenoms with higher effectiveness and broader neutralizing capacity.

Comparative venomics of Brazilian coral snakes: Micrurus frontalis, Micrurus spixii spixii, and Micrurus surinamensis.

A comparative venom proteomic analysis of the Brazilian southern coral snake, M. frontalis, the Amazon coral snake M. spixii spixii, and the aquatic coral snake M. surinamensis is reported. Venoms from M. frontalis and M. s. spixii were composed mainly (>90% of the total venom proteome) by 3FTxs and PLA2s in different proportions, and minor proteins from 2 to 5 protein families. Conversely, the aquatic coral snake expressed a streamlined (95%) 3FTx venom with low abundance (4.2%) of PLA2 molecules. A compositional-lethal activity for natural prey correlation analysis suggests that M. surinamensis venom may has evolved under strong pressure to quickly immobilize aquatic prey. On the other hand, venoms from M. frontalis and M. s. spixii, whose diet consist mainly of amphisbaenians and colubrid snakes, may have been shaped through balancing selection. Our work provides strong evidence for the occurrence in M. frontalis venom, but not in those from M. s. spixi and M. surinamensis, of a KUN-PLA2 complex homologue to heterodimeric venom toxins from some long-tailed monadal coral snakes that target acid-sensing receptors ASIC1a/2 evoking pain. The M. frontalis protein would represent the first example of a KUN-PLA2 heterodimer in a South American short-tailed triadal coral snake venom.

New insights into the phylogeographic distribution of the 3FTx/PLA2 venom dichotomy across genus Micrurus in South America.

Micrurus is a monophyletic genus of venomous coral snakes of the family Elapidae. The ~80 recognized species within this genus are endemic to the Americas, and are distributed from southeastern United States to northern Argentina. Although relatively few bites are recorded due to their reclusive nature, semi-fossorial habits, and their occurrence in sparsely populated areas, coral snakes possess powerful venoms that target the cholinergic system and, if early treatment is missed, can cause neuromuscular paralysis, respiratory failure, and death by asphyxiation within hours of envenoming. The to-date proteomically characterized 18 micrurine venoms exhibit a puzzling phenotypic dichotomy, characterized by the toxin arsenal being dominated either by pre-synaptically acting PLA2s or post-synaptic 3FTxs, and a general, but imperfect, distributional pattern of these venom phenotypes along the North-South axis of the American continent. The lack of perfect phylogenetic clustering suggests that phylogeny may not be the sole factor driving the evolution of the divergent venom phenotypes across Micrurus venoms. To shed new light on the origin and expression pattern of the 3FTx/PLA2 venom dichotomy, we have conducted a comparative proteomics analysis of venoms from the Brazilian ribbon coral snake, Micrurus lemniscatus carvalhoi, sourced from different localities in the Brazilian states of São Paulo; the Caatinga coral snake, M. ibiboboca, from central Bahia state (Brazil); two Micrurus specimens of uncertain taxonomy collected in the Brazilian states of Alagoas and Rio de Janeiro; and the Western ribbon coral snake, M. l. helleri, from Leticia, the southernmost town of the Colombian Department of Amazonas. Venoms from São Paulo and Rio de Janeiro showed 3FTx-predominant phenotypes, while in venoms from Leticia, Alagoas and Bahia PLA2s represented the major toxin family. Comparative venom proteomics suggests that both Micrurus venom phenotypes exhibit a high degree of toxin evolvability. Mapping the 3FTx/PLA2 dichotomy across the Americas points to a phylogeographic pattern for venom phenotypes consistent with, but more complex than, the North-South distribution hypothesis anticipated in previous investigations. BIOLOGICAL SIGNIFICANCE: New World coral snakes (Micrurus: Elapidae) produce potent venoms that target pre- and post-synaptically cholinergic nerve terminals resulting in neuromuscular paralysis, and in severe envenomings, may lead to death from asphyxiation by respiratory arrest. Presynaptic ß-neurotoxins of group IA PLA2 protein subfamily and postsynaptic α-neurotoxins with 3FTx fold are the major components (>80%) of coral snake venoms. Micrurine venoms exhibit a puzzling phenotypic venom dichotomy, characterized by the dominant expression of either α- or ß-neurotoxins. The distribution of these alternative compositional profiles has been fragmentarily studied both across Micrurus phylogeny and along the North-South axis of the genus radiation in the American continent, from southern United States to Northern Argentina. The unpredictability of the neurotoxin profile across the distribution range of the coral snakes represents a difficulty for applying the most appropriate treatment upon a coral snakebite. A deep knowledge of the phylogeographic distribution and the evolution of dichotomic Micrurus venoms would be useful for tracing the evolutionary path to their present day phenotypes, rationalizing the patchy cross-reactivity of current Micrurus antivenoms, and improving the efficacy of antivenoms to neutralize coral snake envenomings.

Factors that can influence the survival rates of coral snakes (Micrurus corallinus) for antivenom production

Envenoming and deaths resulting from snakebites are a particularly important public health problem in rural tropical areas of Africa, Asia, Latin America, and New Guinea. In 2015, The Lancet highlighted snake-bite envenoming as a neglected tropical disease and urged the world to increase antivenom production. In Brazil, around 20,000 snakebites occur per year affecting mostly agricultural workers and children, of which 1% is caused by coral snakes (Micrurus sp.). Although human envenoming by coral snakes is relatively rare due to their semifossorial habits and nonaggressive behavior, they are always considered severe due to the neurotoxic, myotoxic, hemorrhagic, and cardiovascular actions of their venom, which is highly toxic when compared to the venom of other Brazilian venomous snakes as Bothrops sp. (pit vipers), Crotalus sp. (rattlesnakes), and Lachesis sp. (bushmasters). The production of antivenom serum is an important public health issue worldwide and the maintenance of venomous snakes in captivity essential to obtain high-quality venom. Though more than 30 species of Brazilian coral snakes exist, the specific antivenom serum produced with the venom of two species, Micrurus corallinus and M. frontalis, is able to neutralize the accidents caused by the genus in general. M. corallinus is considered a difficult species to maintain in captivity and concerned about this difficulty the Laboratory of Herpetology (LH) at Instituto Butantan, over the last 10 yr, has given special attention to its maintenance in captivity. In more than 20 yr of maintenance, LH has made some changes to improve Micrurus captive husbandry and welfare. The objective of this study was to verify the factors influencing the survival rates of coral snakes in captivity through data generated from 289 M. corallinus from the LH snake facility in the last 10 yr. We observed that survival rates increased significantly with the improvement of nutritional adequacy that included freezing food items before offering them to coral snakes, as well as the development of a new pasty diet to force-feed anorexic animals. Another important factor responsible for increasing life expectancy was the shift of the cage's substrate from Sphagnum to bark in 2010, aiding in the eradication of Blister Disease, which used to be responsible for the death of several coral snakes in previous years.

Mordedura por víbora de coral (Micrurus altirostris): primer caso en Uruguay / Coral snake bite (Micrurus altirostris): first case in Uruguay

Las mordeduras por ofidios del género Micrurus son infrecuentes a nivel mundial. En Uruguay los emponzoñamientos son exclusivamente por Bothrops alternatus y B. pubescens (crucera y yarará). Desde 1986 la notificación de casos de ofidismo es obligatoria ante el Centro de Información y Asesoramiento Toxicológico (CIAT), no habiéndose registrado casos por mordedura de Micrurus altirostris hasta este reporte clínico. Se presenta el primer caso clínico de mordedura por víbora de coral (Micrurus altirostris) en nuestro país, destacándose la gravedad del mismo dada la neurotoxicidad que presentó evolucionando a parálisis respiratoria que requirió ventilación mecánica invasiva. Buena evolución con el sostén de funciones vitales implementado, no requiriendo neostigmina, logrando extubación y reversión completa del cuadro al cuarto día. El antídoto de este emponzoñamiento (suero antielapídico) presenta limitada disponibilidad a nivel mundial, no contando con el mismo en nuestro país, por lo que en casos graves, particularmente con falla respiratoria, la asistencia ventilatoria mecánica es el principal pilar terapéutico. (AU)

Micrurus snakebites are rather unusual globally. In Uruguay, poisoning cases are exclusively caused by Bothrops alternatus and B. pubescens ("crucera" and "yarará" - crossed pit viper). Reporting poisoning to the Poison Information and Advice Service is mandatory since 1986, there being no cases reported of Micrurus altirostris bites until this clinical report. This study presents the first clinical case of coral snake bite (Micrurus altirostris) in our country, emphasizing its severity given the neurotoxicity that evolved into respiratory paralysis requiring invasive mechanical ventilation. Life support implemented resulted in a good evolution, no neostigmine being required, extubation and complete reversal of the clinical symptoms being achieved after four days. Availability of the poisoning antidote (antielapidic serum) is limited around the world, and it cannot be found in our country. Thus, in severe cases, in particular with respiratory failure, mechanical ventilation is the main therapeutic pillar.

As picadas por ofídios do género Micrurus são pouco frequentes em todo o mundo. No Uruguai os envenenamentos são exclusivamente por Bothrops alternatus e B. pubescens ("urutu ou cruzeiro" e "jararaca pintada"). Desde 1986 a notificação de casos de ofidismo ao Centro de Información y Asesoramiento Toxicológico (CIAT) é obrigatória, não havendo registros por picada de Micrurus altirostris até o momento da descrição deste caso clínico. Apresenta-se o primeiro caso clínico de picada por cobra coral (Micrurus altirostris) no país, destacando-se a gravidade do mesmo devida à neurotoxicidade que apresentou e que evoluiu a paralisia respiratória sendo necessária realizar ventilação mecânica invasiva. A evolução foi boa com as medidas de suporte vital implementadas, não sendo necessária a utilização de neostigmina, com extubação e reversão completa do quadro no quarto dia. A disponibilidade do antídoto para este tipo de envenenamento (soro antielapídico) é limitada em todo o mundo não estando disponível no país por isso, especialmente nos casos graves com insuficiência respiratória, a ventilação mecânica é o principal pilar terapêutico.

Coral snake bites (Micrurus spp.) in Brazil: a review of literature reports.

CONTEXT: In the Americas, the main representatives of the family Elapidae are coral snakes of the genus Micrurus, of which 33 species are in Brazil. They are the smallest cause of venomous snakebite in Brazil. We analyzed literature reports of coral snake bites in Brazil from 1867 to 2014, and provide a brief review of case series and reports of coral snake bites in the Americas in general. METHODS: Only reports with clinical descriptions of envenomation were included. The variables recorded included identification of the offending snake, patient's age, sex, bite site, clinical manifestations, treatment, including antivenom and anticholinesterase drugs, and general evolution of the cases. 30 published reports describing bites caused by Micrurus spp. in Brazil were identified and involved 194 distinct cases. Since no information on the clinical manifestations was available in 44 cases, the analysis was restricted to 25 reports (150 cases). RESULTS: Most patients were from southern (61.3%; primarily Santa Catarina state, 60%) and southeastern (20%) Brazil and were male (70.7%), with a median age of 27 years (interquartile interval = 18 to 40 years). The offending snakes were described in 59 cases (M. corallinus 36, M. frontalis 12, M. lemniscatus 5, M. hemprichi 2, M. filiformis 1, M. ibiboboca 1, M. spixii 1 and M. surinamensis 1); in 22 cases only the genus (Micrurus spp.) was reported. Of the 143 cases in which the bite site was recorded, most involved the hands (46.2%) and feet (26.6%). The main clinical features were local numbness/paresthesia (52.7%), local pain (48%), palpebral ptosis (33.3%), dizziness (26.7%), blurred vision (20.7%), weakness (20%), slight local edema (16%), erythema (16%), dysphagia (14.7%), dyspnea (11.3%), inability to walk (10.7%), myalgia (9.3%), salivation (8%) and respiratory failure (4.3%). Fang marks were described in 47.3% of cases and 14% of bites were classified as asymptomatic. A slight increase in total blood creatine kinase was reported in 3 children, suggesting mild myotoxicity. Therapeutic procedures included coral snake antivenom (77.3%), anticholinesterase drugs (6%), and mechanical ventilation (3.3%). Two patients reported in 1933 developed paralysis/respiratory failure and died 6 h and 17 h post-bite. Four more deaths probably caused by coral snakes were reported (2 in 1867, 1 in 1959, 1 in 1962), but no clinical information was available. DISCUSSION: Neuromuscular blockade was the hallmark of systemic envenomation by Micrurus spp., with signs of myasthenia such as weakness and ptosis that may evolve to paralysis and respiratory failure. Local features, mainly numbness/paresthesia and pain, were frequently reported, with the pain being intense in some cases. Although myotoxicity has been detected in experimental studies with Micrurus spp. venoms, few human reports described laboratory findings compatible with myotoxicity. CONCLUSION: Most coral snake bites reported in Brazil were caused by M. corallinus and M. frontalis, with several patients showing signs of acute myasthenia. Serious complications such as paralysis with respiratory failure were observed but comparatively rare. The deaths occurred where respiratory support (mechanical ventilation) was unavailable when needed.

Envenomation by Micrurus coral snakes in the Brazilian Amazon region: report of two cases / Envenenamento por coral do gênero Micrurus na Amazônia brasileira: relato de dois casos

Two cases of proven coral snake bites were reported in Belém, Pará State, Brazil. The first case was a severe one caused by Micrurus surinamensis. The patient required mechanical ventilation due to acute respiratory failure. The second case showed just mild signs of envenomation caused by Micrurus filiformis. Both patients received specific Micrurus antivenom and were discharged without further complications. Coral snake bites are scarcely reported in the Amazon region and there is a broad spectrum of clinical manifestations, varying from extremely mild to those which may rapidly lead to death if the patient is not treated as soon as possible.

Dois acidentes por coral verdadeira são descritos em Belém, Pará. O primeiro caso foi decorrente de envenenamento por Micrurus surinamensis, no qual a vítima necessitou ventilação mecânica por insuficiência respiratória. O segundo, causado por Micrurus filiformis, apresentou apenas manifestações leves. Ambos os pacientes receberam soro antielapídico específico e evoluíram sem complicações. Acidentes por coral verdadeira na região Amazônica são raramente descritos e podem cursar com um largo espectro de alterações, que variam desde quadros de envenenamento muito leves até manifestações com risco de óbito.

How many studies are necessary to compare niche-based models for geographic distributions? Inductive reasoning may fail at the end / Quantos estudos ainda serão necessários para avaliar modelos de distribuição geográfica baseados em modelagem do nicho? Um pensamento indutivo pode estar fadado ao fracasso

The use of ecological niche models (ENM) to generate potential geographic distributions of species has rapidly increased in ecology, conservation and evolutionary biology. Many methods are available and the most used are Maximum Entropy Method (MAXENT) and the Genetic Algorithm for Rule Set Production (GARP). Recent studies have shown that MAXENT perform better than GARP. Here we used the statistics methods of ROC - AUC (area under the Receiver Operating Characteristics curve) and bootstrap to evaluate the performance of GARP and MAXENT in generate potential distribution models for 39 species of New World coral snakes. We found that values of AUC for GARP ranged from 0.923 to 0.999, whereas those for MAXENT ranged from 0.877 to 0.999. On the whole, the differences in AUC were very small, but for 10 species GARP outperformed MAXENT. Means and standard deviations for 100 bootstrapped samples with sample sizes ranging from 3 to 30 species did not show any trends towards deviations from a zero difference in AUC values of GARP minus AUC values of MAXENT. Ours results suggest that further studies are still necessary to establish under which circumstances the statistical performance of the methods vary. However, it is also important to consider the possibility that this empirical inductive reasoning may fail in the end, because we almost certainly could not establish all potential scenarios generating variation in the relative performance of models.

A utilização de modelos de nicho ecológico (ENM) para gerar distribuições geográficas potenciais de espécies tem aumentado rapidamente nas áreas de ecologia, biologia da conservação e biologia evolutiva. O Método de Máxima Entropia (MAXENT) e o Algoritmo Genético para Produção de Conjunto de Regras (GARP) estão entre os métodos mais utilizados, e estudos recentes têm atribuído ao MAXENT um melhor desempenho no processo de modelagem com relação ao GARP. Neste trabalho, foram utilizados os métodos estatísticos ROC - AUC (area under the Receiver Operating Characteristics curve) e de reamostragem (bootstrap) para avaliar o desempenho do GARP e MAXENT em gerar modelos de distribuição potencial para 39 espécies de cobras corais do Novo Mundo. Os resultados mostraram que os valores de AUC para o GARP variaram de 0,923 a 0,999, enquanto que para o MAXENT variaram de 0,877 a 0,999. Em geral, as diferenças de AUC entre os dois métodos foram pequenas, embora o GARP tenha apresentado melhor desempenho que o MAXENT para 10 espécies. Valores de média e desvio padrão de 100 amostras variando de 3 a 30 espécies não revelaram qualquer tendência de desvio em relação à diferença zero entre valores de AUC do GARP menos valores de AUC do MAXENT. Estes resultados sugerem que mais estudos serão necessários para determinar sob quais circunstâncias o desempenho estatístico dos modelos varia, embora seja importante considerar também a possibilidade de que argumentações empírico-indutivas em favor de um ou outro método podem falhar, já que é quase impossível estabelecer todos os cenários potenciais causadores de variação no desempenho dos modelos.

How many studies are necessary to compare niche-based models for geographic distributions? Inductive reasoning may fail at the end / Quantos estudos ainda serão necessários para avaliar modelos de distribuição geográfica baseados em modelagem do nicho? Um pensamento indutivo pode estar fadado ao fracasso

The use of ecological niche models (ENM) to generate potential geographic distributions of species has rapidly increased in ecology, conservation and evolutionary biology. Many methods are available and the most used are Maximum Entropy Method (MAXENT) and the Genetic Algorithm for Rule Set Production (GARP). Recent studies have shown that MAXENT perform better than GARP. Here we used the statistics methods of ROC - AUC (area under the Receiver Operating Characteristics curve) and bootstrap to evaluate the performance of GARP and MAXENT in generate potential distribution models for 39 species of New World coral snakes. We found that values of AUC for GARP ranged from 0.923 to 0.999, whereas those for MAXENT ranged from 0.877 to 0.999. On the whole, the differences in AUC were very small, but for 10 species GARP outperformed MAXENT. Means and standard deviations for 100 bootstrapped samples with sample sizes ranging from 3 to 30 species did not show any trends towards deviations from a zero difference in AUC values of GARP minus AUC values of MAXENT. Ours results suggest that further studies are still necessary to establish under which circumstances the statistical performance of the methods vary. However, it is also important to consider the possibility that this empirical inductive reasoning may fail in the end, because we almost certainly could not establish all potential scenarios generating variation in the relative performance of models.(AU)

A utilização de modelos de nicho ecológico (ENM) para gerar distribuições geográficas potenciais de espécies tem aumentado rapidamente nas áreas de ecologia, biologia da conservação e biologia evolutiva. O Método de Máxima Entropia (MAXENT) e o Algoritmo Genético para Produção de Conjunto de Regras (GARP) estão entre os métodos mais utilizados, e estudos recentes têm atribuído ao MAXENT um melhor desempenho no processo de modelagem com relação ao GARP. Neste trabalho, foram utilizados os métodos estatísticos ROC - AUC (area under the Receiver Operating Characteristics curve) e de reamostragem (bootstrap) para avaliar o desempenho do GARP e MAXENT em gerar modelos de distribuição potencial para 39 espécies de cobras corais do Novo Mundo. Os resultados mostraram que os valores de AUC para o GARP variaram de 0,923 a 0,999, enquanto que para o MAXENT variaram de 0,877 a 0,999. Em geral, as diferenças de AUC entre os dois métodos foram pequenas, embora o GARP tenha apresentado melhor desempenho que o MAXENT para 10 espécies. Valores de média e desvio padrão de 100 amostras variando de 3 a 30 espécies não revelaram qualquer tendência de desvio em relação à diferença zero entre valores de AUC do GARP menos valores de AUC do MAXENT. Estes resultados sugerem que mais estudos serão necessários para determinar sob quais circunstâncias o desempenho estatístico dos modelos varia, embora seja importante considerar também a possibilidade de que argumentações empírico-indutivas em favor de um ou outro método podem falhar, já que é quase impossível estabelecer todos os cenários potenciais causadores de variação no desempenho dos modelos.(AU)