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Snakebite envenoming represents an important Neglected Tropical Disease (NTD) that mainly affects tropical and subtropical developing countries according to the World Health Organization (WHO). As a priority issue in the tropics, it is estimated that accidental encounter between snakes and humans is the leading cause of morbidity and mortality among all NTDs in the world. In Brazil, an extremely diverse country with continental dimensions, snakebite envenoming is the second leading cause of reported human envenoming. Treating the disease has been an unprecedented challenge for Brazilian Health Systems for decades. Despite access to Antivenom therapy and distributing it free of charge across the country, Brazil faces numerous issues regarding the notification process and accurate treatment targeting for at-risk populations. Thus, this study aimed to identify the temporal epidemiological dynamics of accidents caused by Bothrops snakes in Brazil, the country's major group of venomous snakes, based on secondary information from the online database provided by The Brazilian Notifiable Diseases Information System (SINAN). For this purpose, reported Bothrops snakebites between 2012 and 2021 were counted, then the data were analyzed. We looked at the frequency, occurrence, mortality rates, case fatality rate (CFR), age and gender distribution, and the time lapse between the incident and the initiation of Antivenom therapy. The data were also organized considering regional variations of the country. Throughout the studied period, a total of 202,604 cases of envenoming caused by Bothrops spp. were notified, resulting in 766 fatalities. These accidents were found to occur in variable proportions across different regions in Brazil, with notable concentrations observed in the North, Northeast, and Southeast regions. The epidemiological profile of patients varied greatly between the regions, revealing that snake envenoming is much more a social, economic, and ecological problem than a medical one. In conclusion, our study provides an overview of the clinical and epidemiological profile of envenoming by Bothrops snakes in Brazil. Notably, this is the first study to present such information in a country as vast and diverse as Brazil, encompassing a comparative analysis of its regions using SINAN data, that proves to be a very useful national tool to improve the control and management of envenoming., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 da Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Diffusion weighted imaging is a widely used imaging technique for the assessment of white matter using tractography. Nevertheless, due to practical constraints such as limited acquisition times, differences in scanning methods and physical artifacts, these images must be processed by image correction algorithms in order to produce reliable results. State-of-the art susceptibility correction algorithms such as FSL's TOPUP algorithm typically requires at least two images acquired with no diffusion encoding (b=0) in the regular and reverse phase encoding directions, commonly known as double-blip acquisitions, in order to calculate an undistorted volume. Since not all imaging protocols include a double-blip acquisition, they cannot take advantage of these state-of-the art distortion correction algorithms. A new approach based on a Synthetic b-0 Distortion Correction (Synb0-DisCo) has been tested with favourable results. Synb0-DisCo has proven to reduce variation in diffusion modeling creating a synthetic b-0 image to complement the single phase encoding b0 image. In this study, we aim to assess if there are any significant differences in Synb0-DisCo's efficacy resulting from different b-values. To observe critical metrics in the performance of susceptibility correction algorithms we use a 20 healthy subject database from project larynx to create four image sets containing: raw images, single phase encoding eddy correction, double phase encoding eddy correction and one single phase encoding plus a synthetic Synb0-DisCo image eddy correction. From this four image sets we then obtained the mean squared error (MSE) and mutual information (MI). We observed a diminished mean in the MSE, along a smaller dispersion, in the raw image set (Mean: 0.0306; C.I.[0.0369,0.024]) in comparison to the Synb0 image set (Mean: 0.0130; C.I.[0.0194, 0.0067]) We also observe a shift in the MSE depending on the b-value, where b-0 incurs the least MSE which does not occur in b-1000 and b-2000. This effect is lessened in the Synb0 image set. In absence of double phase encoding b-0 image, Synb0-DisCo proves to be a reliable algorithm to improve susceptibility distortion correction.

Snakebite is a universally neglected public health problem. It victimizes approximately 2.5 million people annually and kills around 125 thousand. In Brazil, the Bothrops genus is responsible for 87% of the envenoming. The species Bothrops erythromelas is endemic in the northeast region. Its venom induces local haemorrhage, coagulopathy, oedema, and necrosis and can lead to permanent disability or death. The in vitro effects of Bothrops erythromelas venom (BeV) on thioglycollate-elicited macrophages were investigated in this study. At non-cytotoxic concentrations, BeV did not interfere with the adhesion and detachment of thioglycollate-elicited macrophages. However, BeV induced lipid body formation and the activation of respiratory burst and TNF-α, but not IL-1β and IL-6. The study aimed to extend the knowledge on the mechanism of action of BeV and its contribution toward a better characterisation of macrophage functionality under the action of Bothrops venom., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Accidents by venomous animals are discussed under the historical perspective of state actions. Considered as neglected diseases, they cause social and economic losses in the working age population from rural areas of poor countries, as few of them have public health policies for adequate prophylaxis and treatment; in fact, the largest life losses occur in Africa and Asia. The 46 world producers of antivenin do not meet the global needs, making access to treatment difficult, even in countries with own production. Notification systems lead to inaccurate surveillance surveys and antivenin needs. Despite mandatory notification, Brazil lacks robust databases with full open access in order to allow the timely distribution of antivenin for quality care of these patients. Progress has been made in diagnostic testing, but its application in poor areas is not feasible due to high costs. Improvements in quality antivenin production through good laboratory practices and manufacturing minimize unsatisfactory results of treatments carried out with products of dubious origin. Antivenin development using biotechnology and well-designed clinical trials are key for the treatment of envenoming by agents phylogenetically related from different regions (continental or universal antivenins). International partnerships are fundamental, besides regulatory stocks, similarly to those adopted for vaccines, to supply world demand. The qualification of antivenin will certainly minimize treatment mistakes. Government support to research is a driving force and the most efficient tool for preserving life and avoiding social security surcharges, particularly in developing countries.

This review discusses studies on the venom of Bothrops erythromelas published over the past 36 years. During this period, many contributions have been made to understand the venomous snake, its venom, and its experimental and clinical effects better. The following chronological overview is based on 29 articles that were published between 1979 and 2015, with emphasis on diverse areas. The complexity of this task demands an integration of multidisciplinary research tools to study toxinology. This science is in need of renewed conceptual and experimental platforms aimed at obtaining a profound understanding of the highly complex pathophysiology of snakebite envenoming and toxins isolated from snakes.

The Caatinga lancehead, Bothrops erythromelas, is a medically relevant species, responsible for most of the snakebite accidents in most parts of its distribution range in northeastern Brazil. The spectrum and geographic variability of its venom toxins were investigated applying a venomics approach to venom pools from five geographic areas within the Caatinga ecoregion. Despite its wide habitat, populations of B. erythromelas from Ceará, Pernambuco, Juazeiro, Paraiba, and Ilha de Itaparica exhibit highly conserved venom proteomes. Mirroring their compositional conservation, the five geographic venom pools also showed qualitatively and quantitatively overlapping antivenomic profiles against antivenoms generated in Vital Brazil (BR) and Clodomiro Picado (CR) Institutes, using different venoms in the immunization mixtures. The paraspecificity exhibited by the Brazilian SAB and the Costa Rican BCL antivenoms against venom toxins from B. erythromelas indicates large immunoreactive epitope conservation across genus Bothrops during the last ~14 million years, thus offering promise for the possibility of generating a broad-spectrum bothropic antivenom. Biological Significance Accidental snakebite envenomings represent an important public health hazard in Brazil. Ninety per cent of the yearly estimated 20-30,000 snakebite accidents are caused by species of the Bothrops genus. Bothrops erythromelas, a small, moderately stocky terrestrial venomous snake, is responsible for most of the snakebite accidents in its broad distribution range in the Caatinga, a large ecoregion in northeastern Brazil. To gain a deeper insight into the spectrum of medically important toxins present in the venom of the Caatinga lancehead, we applied a venomics approach to define the proteome and geographic variability of adult B. erythromelas venoms from five geographic regions. Although intraspecific compositional variation between venoms among specimens from different geographic regions has long been appreciated by herpetologists and toxinologists as a general feature of highly adaptable and widely distributed snake species, the five B. erythromelas populations investigated exhibit highly conserved venom proteomes. The overall toxin profile of the Caatinga lancehead's venom explains the local and systemic effects observed in envenomations by B. erythromelas. The five geographic venom pools sampled also showed qualitatively and quantitatively overlapping antivenomic profiles against antivenoms generated using different bothropic venoms in the immunization mixtures. The large immunoreactive epitope conservation across genus Bothrops offers promise for the generation of a broad-spectrum bothropic antivenom., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: The presence of Rhodnius prolixus in palms on the eastern plains area of Colombia provide a high risk for infection with Trypanosoma cruzi. Intensive surveillance of the palm tree habitat are necessary to confirm the presence of bugs and provide evidence that this habitat is a source of house infestations., Objective: The infestation by R. prolixus in the palm, Attalea butyracea, was investigated near homes for assessment of risk., Materials and Methods: Palms were examined for Rhodnius bugs adjacent to rural housing in the eastern plains provinces of Casanare and Arauca, Colombia. Bait traps were used as well as an active search by the investigators and a community watch program to collect intradomiciliary triatomine bugs. Collected species were identified by morphological criteria,and natural T.cruzi infections in the triatomine bugs were detected by the PCR technique., Results: In 111 of 172 (64.5%) palms (A. butyracea) inspected, 529 nymphs and adults of R. prolixus and 5 nymphs of Eratyrus mucronatus were collected. The A. butyracea were located within 500 m of housing. In the same period, 132 R. prolixus and specimens of the triatomine species Psammolestes arthuri,Cavernicola pilosa, Triatoma maculata, Panstrongylus geniculatus were collected inside houses. Twenty nymphs of E. mucronatus were found in a pile of bricks on the porch of a home. Natural infection of T. cruzi was detected in 28.8% of R. prolixus from palm trees and 30.0% inside houses., Conclusions: A new epidemiological scenario of transmission of Chagas disease was revealed, characterized by high rates of infestation of R. prolixus in palms near houses with frequent intrusion into houses. In designing measures to prevent Chagas disease, the association of palm trees, triatomine bugs and housing proximity is a significant consideration.

Introduction: Snake envenomings are a health problem in rural areas of tropical and subtropical countries, but little is known regarding the immune response presented by bitten individuals. The IgM production of patients bitten by Bothrops erythromelas snake was analyzed to identify the effectiveness of treatment in this type of envenomation., Methods: Bothrops erythromelas venom was submitted to electrophoresis and transferred to a nitrocellulose sheet, following incubation with patients' sera., Results: A 38 KDa protein was detected before and 24 h after therapy., Conclusions: The result suggests that this protein could be used as a marker for individuals envenomed by Bothrops. erythromelas.

Objectives: Despite improvements in the surgical management of neonates with the hypoplastic left heart syndrome and its variants, there is a subset of children who have a high predicted mortality. We have analyzed and report our results with the hybrid approach in the management of these high-risk patients., Methods: Children identified by our selection criteria underwent the initial hybrid procedure performed in the catheterization laboratory. This consists of surgical banding of the branch pulmonary arteries and stenting of the arterial duct. This was followed 3 to 6 months later by the combined stage I and II Norwood operation or biventricular repair., Results: Between December 2005 and May 2008, 21 neonates were selected for the hybrid procedure, of whom 16 had typical hypoplastic left heart syndrome. The remaining 5 neonates had severe aortic stenosis with borderline left ventricular dimensions or poor left ventricular function at presentation. Four neonates had a virtually intact interatrial septum and required urgent intervention immediately after birth. There were 6 deaths as inpatients or up to 30 days after the procedure and 1 interstage death before the combined stage I and II operation. Thus far, of 12 babies who have undergone the next operation, 9 have had the combined stage I and II operation and 3 have had a biventricular repair. Two of these 12 babies have died after the combined stage I and II operation., Conclusion: A hybrid approach may be a valuable alternative to the management of high-risk neonates with hypoplastic left heart syndrome and its variants., (2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Introduction: The current chemotherapy for Chagas disease is unsatisfactory with only two drugs available for treatment. Research to discover new drugs for Chagas disease is urgent. Hexadecyl-phosphocholine (HPC, miltefosine) has been demonstrated to have in vitro activity against Trypanosoma cruzi parasites, but its activity on different Colombian T. cruzi strains is not known., Objective: To evaluate the in vitro susceptibility of T. cruzi strains isolated from humans and vectors in Santander, Colombia. to miltefosine, nifurtimox and benznidazole., Materials and Methods: Eight T. cruzi Colombian strains and three reference strains (Esmeraldo, SilvioX10 and Y) were studied. Drug activities against extracellular epimastigotes and intracellular amastigotes were determined by microscopic counting. The results were expressed as the concentrations that inhibited 50% and 90% growth (IC50 and IC90)., Results: For miltefosine a similar range of drug activity was observed against all the Colombian strains, all parasites being more susceptible to miltefosine than to the reference drugs. The intracellular amastigotes were more susceptible to miltefosine (IC50 0.08 to 0.63 microM and IC90 0.21 to 2.21 microM) than extracellular forms (IC50 <0.92 to 2.29 microM and IC90 1.38 to 4.76 microM). For reference drugs, parasites were more susceptible to nifurtimox than to benznidazole and some differences in activity of benznidazole between T. cruzi strains was observed., Conclusions: The results showed the significant in vitro activity of miltefosine against T. cruzi stages, and the expected results for the reference drugs. Further in vivo studies with miltefosine are planned.

Introduction: Between 1998 and 2000, the occurrence of 8 cases of American visceral leishmaniasis in children from a recently established human settlement in Guatiguará, in the municipality of Piedecuesta (Santander, Colombia) indicated the possible presence of Leishmania transmission in this locality. This observation motivated the current entomological investigation., Objectives: To determine the relative frequency of Lutzomyia longipalpis inside houses and outdoors, and the natural infection of this vector with Leishmania spp., Materials and Methods: CDC light traps were used for sampling inside houses and outdoors, and sand flies were collected on human volunteers and domestic animals, and in resting places, during the period from May 1999 through September 2000. Natural infection was determined by PCR, in pools of female Lutzomyia longipalpis., Results: A total of 7,391 phlebotomine sand flies were collected. The predominant species was Lutzomyia longipalpis (Lutz & Neiva), representing 99.5% of captures. In the sand flies collected with CDC light traps, L. longipalpis was more frequently collected indoors than outdoors (p = 0.0001). The total rate of natural infection was 1.93% and a positive correlation was observed between months with higher abundance and the number of infected females entering human dwellings., Conclusions: The results indicate that in Guatiguará Lutzomyia longipalpis, shows marked tendency for the indoors, which has important implications for leishmaniasis transmission. Furthermore, transmission risk is increased during the months of higher abundance due to the entry of a higher number of infected females. From the standpoint of control, this behaviour permits the design of strategies to reduce indoor transmission.