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In vivo studies of botulinum neurotoxin type A (BoNT-A) enabled characterization of its activity in the nociceptive sensory system separate from its preferred action in motor and autonomic nerve terminals. However, in the recent rodent studies of arthritic pain which employed high intra-articular (i.a.) doses (expressed as a total number of units (U) per animal or U/kg), possible systemic effects have not been conclusively excluded. Herein we assessed the effect of two pharmaceutical preparations, abobotulinumtoxinA (aboBoNT-A, 10, 20, and 40 U/kg corresponding to 0.05, 0.11, and 0.22 ng/kg neurotoxin) and onabotulinumtoxinA (onaBoNT-A, 10 and 20 U/kg corresponding to 0.09 and 0.18 ng/kg, respectively) injected into the rat knee, on safety-relevant readouts: digit abduction, motor performance and weight gain during 14 days post-treatment.

The i. a. toxin produced dose-dependent impairment of the toe spreading reflex and rotarod performance, which was moderate and transient after 10 U/kg onaBoNT-A and ≤20 U/kg aboBoNT-A doses, and severe and long-lasting (examined up to 14 days) after ≥20 U/kg of onaBoNT-A and 40 U/kg aboBoNT-A. In addition, lower toxin doses prevented the normal weight gain compared to controls, while higher doses induced marked weight loss (≥20 U/kg of onaBoNT-A and 40 U/kg aboBoNT-A).

Commonly employed BoNT-A formulations, depending on the doses, cause local relaxation of the surrounding muscles and systemic adverse effects in rats. Thus, to evade possible toxin unwanted local or systemic spread, careful dosing and motor testing should be mandatory in preclinical behavioral studies, irrespective of the sites and doses of toxin application.

Africa remains one of the regions with the highest incident and burden of snakebite. The goal of the World Health Organization to halve the global burden of snakebite by 2030 can only be achieved if sub-optimal access to antivenoms in the most affected regions is addressed. We identified upstream, midstream, and downstream factors along the antivenom value chain that prevent access to antivenoms in the African region. We identified windows of opportunities that could be utilized to ensure availability, accessibility, and affordability for snakebite endemic populations in Africa. These include implementation of multicomponent strategies such as intensified advocacy, community engagement, healthcare worker trainings, and leveraging the institutional and governance structure provided by African governments to address the challenges identified.

During the production of snake antivenoms, the animals used as immunoglobulin source are subjected to processes that could deteriorate their physical condition. Therefore, these conditions must be carefully designed and validated. In this work, the immunization and bleeding protocols applied to horses used to produce the African polyspecific antivenom EchiTAb-plus-ICP were evaluated regarding their effects on the horses' health. The study focused on horses that had been previously immunized with venoms and then received periodic booster venom injections for antivenom production. It was found that the periodic immunization with 5 mg of a mixture of venoms of Bitis arietans, Echis ocellatus, Dendroaspis polylepis, and Naja nigricollis did not induce systemic signs of envenomation, and only caused mild swelling at the injection site, which did not evolve to abscesses, fistulas, or fibrosis. Three consecutive days of bleeding, collecting 6–8 L of blood per day, and self-transfusing the red blood cells (RBC) in the second and third days, did not induce evident cardiorespiratory alterations. However, this procedure caused significant reductions in RBC, hematocrit, hemoglobin, and total plasma protein values. Seven weeks after bleeding, these parameters were recovered, and horses were ready for the next immunization/bleeding cycle. The intravenous administration of equine albumin, at a dose of 2 g/kg body weight, increased the apparent plasma volume and the albumin concentration. However, this procedure induced early adverse reactions and transient alterations of the serum levels of the enzyme gamma-glutamyl transferase (GGT), thus suggesting some degree of hepatic injury. It was concluded that immunization and bleeding as described in this work do not cause significant clinical alterations in the horse's health, except for a transient drop in some hematological parameters. The albumin-based fluid therapy used does not hasten the recovery after bleeding but instead induces adverse events in the animals.

Snakebite is a public health problem in many countries, with India having the highest number of deaths. Not much is known about the effect of the COVID-19 pandemic on snakebite care. We conducted 20 in-depth interviews with those bitten by venomous snakes through the two waves of COVID-19 (March–May 2020; May–November 2021), their caregivers, health care workers and social workers in two areas (Sundarbans and Hooghly) of West Bengal, India. We used a constructivist approach and conducted a thematic analysis. We identified the following themes: 1. Snakebite continued to be recognised as an acute emergency during successive waves of COVID-19; 2. COVID-19 magnified the financial woes of communities with high snakebite burden; 3. The choice of health care provider was driven by multiple factors and consideration of trade-offs, many of which leaned toward use of traditional providers during COVID-19; 4. Rurality, financial and social disadvantage and cultural safety, in and beyond the health system, affected snakebite care; 5. There is strong and shared felt need for multi-faceted community programs on snakebite.

We mapped factors affecting snakebite care in the three-delay model (decision to seek care, reaching appropriate health facility, receiving appropriate care), originally developed for maternal mortality. The result of our study contextualises and brings forth evidence on impact of COVID-19 on snakebite care in West Bengal, India. Multi-faceted community programs, are needed for addressing factors affecting snakebite care, including during disease outbreaks - thus improving health systems resilience. Community programs for increasing formal health service usage, should be accompanied by health systems strengthening, instead of an exclusive focus on awareness against traditional providers.

The medical humanitarian organization Médecins Sans Frontières (MSF) provides medical care in more than 70 countries and admits more than 7000 cases of snakebite in its facilities each year.

We describe our activities against snakebite in three African countries: Central African Republic, South Sudan and Ethiopia, in which different models of care have been developed. A standard protocol using two different antivenoms depending on the patient's syndrome has been introduced, and a simple blood coagulation test is performed to detect venom-induced coagulopathy. Other services, including surgery for necrotizing wounds, are offered in the facilities where MSF admits a large number of snakebite patients. All services, including provision of antivenom, are offered free-of-charge in MSF-supported facilities. Community-based activities focusing on preventive measures and prompt transport to hospital have been developed in a few MSF projects.

The provision of quality care and treatment, including effective antivenoms, without out-of-pocket payments by the patients, probably explains why MSF has admitted an increasing number of snakebite victims over the last years. This model requires significant resources and monitoring, including regular training of healthcare workers on treatment protocols and a considerable budget for antivenom procurement.

Antivenom is the main treatment for snake envenoming and there are ongoing concerns about availability in resource poor regions of the world. However, effective antivenom treatment for snake envenoming requires more than improved availability of safe and efficacious antivenoms. Most importantly, antivenom must be administered as early as possible, and within 2–6 h of the bite in Australia. At the same time, it is also important that antivenom not be given to all patients indiscriminately with a suspected snakebite, because of the risk of anaphylaxis. Delays in the administration of antivenom are a significant impediment to effective antivenom treatment and can be divided into pre-hospital and in-hospital delays. These range from delays due to remoteness of snakebite, to delays in diagnosis and administration of antivenom once in hospital. In Australia, antivenom is readily available in most hospitals, and a large portion of patients present to hospital within 2 h of the bite. However, there is on average a further delay of 2.5 h before antivenom is administered. Early diagnosis with accurate bedside tests and rapid clinical assessment of patients with snakebite are key to improving the effective use of antivenom.

Snakebite envenoming (SBE) predominantly affects rural impoverished communities that have limited access to immediate healthcare. These communities often hold numerous myths/misbeliefs about snakes and SBE. Moreover, healthcare professionals who practice in rural regions often work in unstable situations with limited medical infrastructure and therefore, lack sufficient knowledge/experience and confidence in the clinical management of SBE. Due to the lack of reliable statistics on the true burden of SBE, developing health policies for this condition by relevant authorities may be difficult. Hence, it is critical to improve awareness about SBE among rural communities, healthcare professionals and health authorities using robust multifaceted community health education approaches. Here, we describe the design, development, implementation, and impact of distinctive community health education approaches that we used in India and Brazil. A wide range of educational tools including information leaflets, posters, pocket guides, learning materials for healthcare professionals and short/long video documentaries were developed in local languages and used to engage with target communities through direct assemblies as well as mass/traditional and social media. Notably, we used diverse methods to determine the impact of our programs in improving awareness, treatment-seeking behaviour, and clinical practice. The people-centred approaches that we used were inclusive and highly impactful in instigating fundamental changes in the management of SBE among rural communities. The resources and approaches presented in this article can be easily adapted for wider use in other countries in order to collectively reduce SBE-induced deaths, disabilities and socioeconomic ramifications.

With the advancements in therapeutics and available treatment options, almost all deaths and permanent disabilities from snakebite envenoming (SBE) are preventable. The challenge lies in implementing these evidence-based treatments and practices across different settings and populations. This study aims to compare data on provider perceptions of SBE care across health systems and cultural contexts to inform potential implementation science approaches. We hypothesize different health systems and cultural contexts will influence specific perceived needs to provide adequate snakebite care within central tenets of care delivery (e.g., cost, access, human resources). We previously conducted exploratory descriptive studies in the US and Brazil in order to understand the experience, knowledge, and perceptions of health professionals treating SBE. In the US, in-depth interviews were performed with emergency physicians from January 2020 to March 2020. In BR, focus group discussions were conducted with health professionals from community health centers at the end of June 2021. The focus group discussions (BR) were originally analyzed through an inductive thematic analysis approach. We conducted a secondary qualitative analysis in which this codebook was then applied to the interviews (US) in a deductive content analysis. The analysis concluded in August 2022. Brazil participants were physicians (n=5) or nurses (n=20) from three municipalities in the State of Amazonas with an average of three years of professional experience. US participants were emergency physicians (n=16) with an average of 15 years of professional experience. Four main themes emerged: 1) barriers to adequate care on the patient and/or community side and 2) on the health system side, 3) perceived considerations for how to address SBE, and 4) identified needs for improving care. There were 25 subthemes within the four themes. These subthemes were largely the same across the Brazil and US data, but the rationale and content within each shared subtheme varied significantly. For example, the subtheme “role of health professionals in improving care” extended across Brazil and the US. Brazil emphasized the need for task-shifting and -sharing amongst health care disciplines, whereas the US suggested specialized approaches geared toward increasing access to toxicologists and other referral resources. Despite similar core barriers to adequate snakebite envenoming care and factors to consider when trying to improve care delivery, health professionals in different health systems and sociocultural contexts identified different needs. Accounting for, and understanding, these differences is crucial to the success of initiatives intended to strengthen snakebite envenoming care. Implementation science efforts, with explicit health professional input, should be applied to develop new and/or adapt existing evidence-based treatments and practices for SBE.

Peroxisomicine A1 (PA1) is a toxin isolated from the Karwinskia genus plants whose target organs are the liver, kidney, and lung. In vitro studies demonstrated the induction of apoptosis by PA1 in cancer cell lines, and in vivo in the liver. Apoptosis has a wide range of morphological features such as cell shrinkage, plasma membrane blistering, loss of microvilli, cytoplasm, and chromatin condensation, internucleosomal DNA fragmentation, and formation of apoptotic bodies that are phagocytized by resident macrophages or nearby cells. Early stages of apoptosis can be detected by mitochondrial alterations. We investigated the presence of apoptosis in vivo at the morphological, ultrastructural, and biochemical levels in two target organs of PA1: kidney and lung. Sixty CD-1 mice were divided into three groups (n = 20): untreated control (ST), vehicle control (VH), and PA1 intoxicated group (2LD50). Five animals of each group were sacrificed at 4, 8, 12, and 24 h post-intoxication. Kidney and lung were examined by morphometry, histopathology, ultrastructural, and DNA fragmentation analysis. Pre-apoptotic mitochondrial alterations were present at 4 h. Apoptotic bodies were observed at 8 h and increased over time. TUNEL positive cells were detected as early as 4 h, and the DNA ladder pattern was observed at 12 h and 24 h. The liver showed the highest value of fragmented DNA, followed by the kidney and the lung. We demonstrated the induction of apoptosis by a toxic dose of PA1 in the kidney and lung in vivo. These results could be useful in understanding the mechanism of action of this compound at toxic doses in vivo.