Broadly-neutralizing monoclonal antibodies are becoming increasingly important tools for treating infectious diseases and animal envenomings. However, designing and developing broadly-neutralizing antibodies can be cumbersome using traditional low-throughput iterative protein engineering methods. Here, we present a new high-throughput approach for the standardized discovery of broadly-neutralizing monoclonal antibodies relying on phage display technology and consensus antigens representing average sequences of related proteins. We showcase the utility of this approach by applying it to toxic sphingomyelinases from the venoms of species from very distant orders of the animal kingdom, the recluse spider and Gadim scorpion. First, we designed a consensus sphingomyelinase and performed three rounds of phage display selection, followed by DELFIA-based screening and ranking, and benchmarked this to a similar campaign involving cross-panning against recombinant versions of the native toxins. Second, we identified two scFvs that not only bind the consensus toxins, but which can also neutralize sphingomyelinase activity of native whole venom in vitro. Finally, we conclude that the phage display campaign involving the use of the consensus toxin was more successful in yielding cross-neutralizing scFvs than the phage display campaign involving cross-panning.

Snakebite envenoming (SBE) is a neglected tropical disease with significant global morbidity and mortality. Even when antivenom is available in low-resource areas, health workers do not receive adequate training to manage SBEs. This study aims to develop and validate a clinical practice guideline (CPG) for SBE management across Brazil. A panel of expert judges with academic and/or technical expertise in SBE management performed content validation. The content validity index (CVI) score was 90% for CPG objectives, 89% for structure and presentation and 92% for relevance and classified the CPG as valid. A semantic validation was performed by analyzing focus group discussions with doctors and nurses from three municipalities of the Brazilian Amazon, after a 5-day meeting during which the CPG was presented. Two central themes emerged: knowledge acquired during the meeting and recommendations for improving the CPG. Based on these results, the CPG was revised into a final version. This study presents the successful development and validation process of a CPG for SBE management, which is targeted to a specific low-resource, high-burden setting. This development and validation process can be adapted to other settings and/or other neglected tropical diseases.

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OBJECTIVE: Snakebite is an emergency which causes local symptoms such as pain and edema around the bite. Systemic symptoms may also develop, such as dizziness or renal failure, and may even cause death. The purpose of this research was to assess the validity and safety of snakebite protocol for surgery when treating snakebite patients.
METHODS: Retrospective research was performed on patients who were admitted after being treated at the emergency center from January 2008 to December 2012. When necessary, debridement was also performed, and 46 of 111 patients (41.4%) underwent debridement. Those who had received debridement without antivenom administration due to a positive skin reaction test were classified as group A, and group B received antivenom and delayed debridement. We reviewed the emergency and admission charts of the patients in each group and recorded and compared their age, sex, bite site, severity of local and general symptoms, time to receive antivenin, and complications.
RESULTS: Of the ten patients (21.7%) in group A, two (66.6%) developed cellulites, and one of them experienced skin necrosis, resulting in a skin graft. In group B, there were 36 patients (78.2%), 19 (52.7%) of whom developed cellulitis. Skin necrosis occurred in two patients, and one of these patients received a skin graft. Compartment syndrome was found in one patient, and fasciotomy and a skin graft were performed.
CONCLUSIONS: The treatment protocol implemented to treat snakebite patients admitted to the emergency center during this research was safely and properly followed during surgical treatment.

BACKGROUND: Snakebite has recently been declared a global public health emergency. Empirical data showing the true burden of snakebite is lacking. Treatment with specific antivenoms is considered the only cure. However, several factors have led to an ongoing antivenom crisis. This study offers recommendations concerning the improvement of antivenom access and control, by providing an overview of the factors limiting the successful implementation of international guidelines within the international industry and state institutions. It further investigates the reasons for the epidemiological knowledge gap regarding snakebites.
METHODS: Data for this study was collected using surveys with closed- and open-ended questions, which allowed for descriptive and thematic analysis, respectively. Participants for this study were selected as follows: 46 manufacturers were contacted from the open-access World Health Organization (WHO) Database for antivenom producers; 23 National Health Authorities (NHAs) of high-burden countries were contacted; and 11 poison centers or experts were randomly contacted.
RESULTS: In total, responses from 6/46 (13%) manufacturers, 10/23 (43%) NHAs, and 3/11 (27%) poison centers were received. The low response rates had a limiting effect on the coverage of this study, allowing only exploratory conclusions to be drawn. Based on the gathered information, a probable reason for the epidemiological knowledge gap is the low priority given to snakebites on public health agendas, driving interest and funding away from research in this field. As a consequence, the ensuing lack in funding is preventing state institutions and manufacturers from implementing international guidelines to the highest standards. Furthermore, manufacturers indicated that international guidelines were often not applicable in the field, lacking technical information and protocols.
CONCLUSIONS: Snakebite ranks low on international public health agendas, and partially due to this low priority, NHAs have shown limited efforts in conducting epidemiological studies, training health workers on snakebite management and creating national snakebite management strategies. The lack of NHA involvement is reflected in poor access to appropriate antivenoms as well as a lack of antivenom regulation. Manufacturers are taking positive steps toward full implementation of international guidelines and are improving quality control procedures. However, in order for international guidelines to become truly useful in the field, more technical guidance is required. This study reflects that there is a general lack of knowledge transfer amongst various actors: most producers, health authorities, and experts expect increased and improved communication and guidance from leading international bodies. Due to the low response rates observed in this study, conclusions drawn herein are not representative of the global situation; yet provide an exploratory insight on the difficulties facing antivenom management.