Bleeding and Thrombosis: Insights into Pathophysiology of Bothrops Venom-Related Hemostasis Disorders.

Toxins from Bothrops venoms targeting hemostasis are responsible for a broad range of clinical and biological syndromes including local and systemic bleeding, incoagulability, thrombotic microangiopathy and macrothrombosis. Beyond hemostais disorders, toxins are also involved in the pathogenesis of edema and in most complications such as hypovolemia, cardiovascular collapse, acute kidney injury, myonecrosis, compartmental syndrome and superinfection. These toxins can be classified as enzymatic proteins (snake venom metalloproteinases, snake venom serine proteases, phospholipases A2 and L-amino acid oxidases) and non-enzymatic proteins (desintegrins and C-type lectin proteins). Bleeding is due to a multifocal toxicity targeting vessels, platelets and coagulation factors. Vessel damage due to the degradation of basement membrane and the subsequent disruption of endothelial cell integrity under hydrostatic pressure and tangential shear stress is primarily responsible for bleeding. Hemorrhage is promoted by thrombocytopenia, platelet hypoaggregation, consumption coagulopathy and fibrin(ogen)olysis. Onset of thrombotic microangiopathy is probably due to the switch of endothelium to a prothrombotic phenotype with overexpression of tissue factor and other pro-aggregating biomarkers in association with activation of platelets and coagulation. Thrombosis involving large-caliber vessels in B. lanceolatus envenomation remains a unique entity, which exact pathophysiology remains poorly understood.

Successful Management of Two Patients with Intracranial Hemorrhage due to Carpet Viper (Echis ocellatus) Envenomation in a Limited-Resource Environment.

The West African carpet viper (Echis ocellatus) causes more deaths than any other snake in sub-Saharan Africa. Carpet viper envenomations are characterized by a venom-induced consumption coagulopathy and systemic bleeding syndrome, in addition to local symptoms of painful progressive swelling and tissue destruction. The highest mortality rate is seen in the final stages of the syndrome, which typically ends with fatal internal bleeding or hemorrhagic shock. We present 2 cases of E ocellatus envenomation with intracranial hemorrhage seen at a rural hospital in Bembèrèkè, Benin, and describe the successful management of these patients in a limited-resource setting. In one case the patient was treated with an ineffective Indian-made antivenom before evaluation by the authors and continued to deteriorate until she was treated with effective antivenom 10 d after the bite. In both cases lumbar puncture was performed for diagnostic or therapeutic purposes with good effect, and both patients made full recoveries without sequelae. These cases demonstrate the remarkable ability of high-quality antivenoms to reverse life-threatening envenomations even in the final stages of the hemorrhagic syndrome and illustrate the dangers posed by low-quality antivenoms that have flooded the market in the developing world.

Persistent Plasmodium falciparum Infection in Women With an Intent to Become Pregnant as a Risk Factor for Pregnancy-associated Malaria.

Background: Pregnant women are more susceptible to Plasmodium falciparum than before pregnancy, and infection has consequences for both mother and offspring. The World Health Organization recommends that pregnant woman in areas of transmission receive intermittent preventive treatment (IPTp) starting in the second trimester. Consequently, women are not protected during the first trimester, although P. falciparum infections are both frequent and harmful. Methods: A cohort of nulligravid women was followed up during subsequent pregnancy. Malaria was diagnosed by means of microscopy and polymerase chain reaction. Parasites were genotyped at polymorphic loci. Results: Among 275 nulligravidae enrolled, 68 women became pregnant and were followed up during pregnancy. Before pregnancy, P. falciparum prevalence rates were 15% by microscopy and 66% by polymerase chain reaction. Microscopic infection rates increased to 29% until IPTp administration, and their density increased by 20-fold. Conversely, submicroscopic infection rates decreased. After IPTp administration, all types of infections decreased, but they increased again late in pregnancy. The risk of infection during pregnancy was higher in women with a microscopic (odds ratio, 6.5; P = .047) or submicroscopic (3.06; P = .05) infection before pregnancy and was not related to the season of occurrence. Most infections during pregnancy were persistent infections acquired before pregnancy. Conclusions: Microscopic and submicroscopic malaria infections were frequent in nulligravid women from south Benin. During the first trimester of pregnancy, microscopic infections were more frequent, with a higher parasite density, and mainly derived from parasites infecting the woman before conception. Preventive strategies targeting nonpregnant women with a desire for conception need to be designed.

Gaston Ramon's Big Four.

When immunology was still in its infancy, Gaston Ramon made several major contributions to humoral immunology [...].

Comprehensive Review of Epidemiology and Treatment of Snakebite Envenomation in West Africa: Case of Benin.

Snakebite envenomation (SBE) constitutes a public health, social, and economic problem affecting poor communities in intertropical and subtropical regions. This review sought to synthesize literature on snakebite envenomation in Benin to highlight research perspectives and strategies for better management of the menace. A literature search performed in multidisciplinary electronic databases showed that the prevalence of SBE is high in Benin, but the incidences, associated morbidities, and mortalities are greatly underestimated. Most snake envenomations are by Echis ocellatus in Northern Benin during the rainy season. Adults involved in agricultural activities are the most affected. The absence of antivenin serum in the most affected areas explains the preference for alternative and traditional medicine as the first-line treatment for SBE in Benin. In conclusion, it would be imperative to revitalize the snakebite reporting system in order to have better epidemiological data and to develop a sustainable national strategy for the control and management of snakebite envenomation.

Snakebites in Cameroon: Tolerance of a Snake Antivenom (Inoserp™ PAN-AFRICA) in Africa in Real-Life Conditions.

Snakebite envenomation (SBE) is a public health issue in sub-Saharan countries. Antivenom is the only etiological treatment. Excellent tolerance is essential in managing SBE successfully. This study aimed to evaluate tolerance of InoserpTM PAN-AFRICA (IPA). It was conducted on fourteen sites across Cameroon. IPA was administered intravenously and repeated at the same dose every two hours if needed. Early and late tolerance was assessed by the onset of clinical signs within two hours and at a visit two weeks or more after the first IPA administration, respectively. Over 20 months, 447 patients presenting with a snakebite were included. One dose of IPA was administered to 361 patients and repeated at least once in 106 patients. No significant difference was shown between the proportion of adverse events in patients who received IPA (266/361, 73.7%) and those who did not (69/85, 81.2%) (p = 0.95). Adverse reactions, probably attributable to IPA, were identified in four (1.1%) patients, including one severe (angioedema) and three mild. All these reactions resolved favorably. None of the serious adverse events observed in twelve patients were attributed to IPA. No signs of late intolerance were observed in 302 patients. Tolerance appears to be satisfactory. The availability of effective and well-tolerated antivenoms would reduce the duration of treatment and prevent most disabilities and/or deaths.

[Role of antivenoms in the treatment of snake envenomation]. / Place de l'immunothérapie dans le traitement actuel des envenimations ophidiennes.

The production of antivenoms, which were long deemed ineffective, dangerous and difficult to use, has improved dramatically. These antibodies (immunoglobulin G) are now fragmented, purified and controlled for their quality, leading to significantly better safety and facilitating their emergency use. Envenomation can result in various syndromes depending on the snake species: Viperidae venoms are highly inflammatory, hemorrhagic and necrotising, while Elapidae venoms can cause fatal respiratory paralysis. However, some Viperidae venoms can lead to asphyxiation similar to that observed in Elapidae envenomation while, conversely, Elapidae bites may be complicated by hemorrhage or necrosis, thus complicating etiologic diagnosis. Symptomatic treatment is complex, often insufficient, and frequently associated with adverse events. In contrast, antivenoms neutralize the venom and accelerate its clearance, thus providing an etiological treatment for envenomation, particularly in remote healthcare facilities in developing countries. Current formulations consist of polyvalent antivenoms covering most of the venomous species present in a specific region. The main limitation is their high cost, and the priority should be to develop new treatment strategies, including more affordable antivenoms, especially in developing countries where they are most needed.

[Sexual behavior and condom use by people living with HIV/AIDS in Gabon]. / Comportements sexuels et usage du préservatif chez les personnes vivant avec le VIH/sida au Gabon.

INTRODUCTION: The HIV/AIDS prevalence rate in Gabon in 2011 was 5% among subjects aged 15 to 49 years. The objective of this study was to describe sexuality and condom use among people living with HIV/AIDS (PLWH) by comparing those living in the capital with those living in two provinces of Gabon: Ogowe-Maritime (Port-Gentil) and Ogowe-Moyen (Lambaréné). METHODS: A 5-month, cumulative, cross-sectional descriptive survey was conducted between May 2009 and September 2010 among PLWH over the age of 18 years, attending Gabon treatment centres and treated with ARVs for at least six months. A simple random sampling method was used to construct this sample. This survey was conducted in seven different centres for PLWH. RESULTS: The survey was conducted among 422 PLWH treated with ARV for at least six months: 284 (67.3%) subjects in Libreville and 138 (32.7%) in the provinces. The F/M sex ratio was 0.71. In this sample, 68% of PLWH reported sexual intercourse at least once during the previous 6 months. 49.5% of PLWH declared that they always used a condom with their main partner (p = 0.0096) and 52.4% declared that they always used a condom with other partners (p < 0.0001). 50.1% of PLWH also reported that their last sexual intercourse during the previous 6 months was with their main partner (p < 0.0001). CONCLUSION: The majority of patients on ARV therapy use condoms with their main partner and with occasional partners. Management and condom use are more effective in Libreville.

COVID-19 impacts on healthcare access in sub-Saharan Africa: an overview.

This overview aimed to describe the situation of healthcare access in sub-Saharan Africa, excluding South Africa, during the COVID-19 pandemic. A PubMed® search from March 31, 2020, to August 15, 2022, selected 116 articles. Healthcare access and consequences of COVID-19 were assessed based on comparisons with months before its onset or an identical season in previous years. A general reduction of healthcare delivery, associated with the decline of care quality, and closure of many specialty services were reported. The impact was heterogeneous in space and time, with an increase in urban areas at the beginning of the pandemic (March-June 2020). The return to normalcy was gradual from the 3rd quarter of 2020 until the end of 2021. The impact of COVID-19 on the health system and its use was attributed to (a) conjunctural factors resulting from government actions to mitigate the spread of the epidemic (containment, transportation restrictions, closures of businesses, and places of entertainment or worship); (b) structural factors related to the disruption of public and private facilities and institutions, in particular, the health system; and (c) individual factors linked to the increase in costs, impoverishment of the population, and fear of contamination or stigmatization, which discouraged patients from going to health centers. They have caused considerable socio-economic damage. Several studies emphasized some adaptability of the healthcare offer and resilience of the healthcare system, despite its unpreparedness, which explained a return to normal activities as early as 2022 while the COVID-19 epidemic persisted. There appears to be a strong disproportion between the moderate incidence and severity of COVID-19 in sub-Saharan Africa, and the dramatic impact on healthcare access. Several articles make recommendations for lowering the socioeconomic consequences of future epidemics to ensure better management of health issues.

[The different models of scientific journals]. / Les différents modèles de revues scientifiques.

Introduction: Scientific journals are the main source of scientific data, ensuring their registration, validation, distribution and archiving. With over 2.6 million scientific articles published each year, the turnover of scientific journals exceeds $25 billion annually. Five publishers share nearly half of this lucrative market. Scientists are the key players in the process, but other stakeholders have gradually been introduced, building various business models whose similarities and differences are described here. Concepts underlying scientific publication: Open access to scientific papers dates back to the scientific and technical revolution of the 17th century. However, its evolution has been considerably boosted by the development of the Internet and the recognition of science as "commons".Scientific integrity is under the control of research institutions to ensure the prevention of fraud and misconduct in the course of scientific production. Usually, the scientific integrity is questioned during the manuscript reviewing process which may result in identification of flaws. Models of scientific publications: In the historical model, readers pay for access to the document. Authors are not remunerated and renounce copyright on their articles to the publisher. The limits of the historical model became clear in the 90s, facing the cost of publishing, reduction in the number of subscribers, development of the Internet and willingness to improve manuscript evaluation.With the development of the Internet and the paradigm of open access, publishers proposed a new model in the 2000s, replacing the cost of access to articles for the reader with the payment of Article Processing Charges (APCs) paid by the author or its institution ("author pays" model). In this model, the content of the article can be freely reproduced and used, provided that the original author is credited. In addition to the evaluation of the manuscript which remains a critical factor, the cost of publication appears inequitable. However, all or part of the APCs may be waived, particularly for authors from low- and middle-income countries.For the past 15 years or so, publishers, learned societies and academic or research institutions (including libraries) have been seeking to publish reliable, open access manuscripts that respect scientific integrity while being affordable for the author.Predatory journals emerged in the late 2000s, taking advantage of the success of the authorpays model to capture APCs. Lacking a proper evaluation process resulting in poor-quality publications, these journals are rejected by most scientific institutions. On the other hand, they are particularly attractive in low- and middle-income countries because of their aggressive commercial practices (insistent invitation to submit a manuscript, low rejection rate, rapid publication, reduced APC, etc.).The purpose of each journal is to secure its economic model. This goes through ensuring its visibility, which is determined by the number of citations (online and social media citations) rather than the quality of the articles published. Peer review: This very old concept has not been widely used until the 20th century. In the historical model, manuscript evaluation is generally carried out by members of the learned society that publishes the journal. Evaluation can be either unblinded, single-blinded (referee is anonymous) or double-blinded (author and referee are anonymous). Several studies have shown that blind procedures do not alter the quality of the evaluation. Since the early 90s, post-publication evaluation has emerged, of which there are several variants. The aim is to shorten times to publication and open up the evaluation process more widely in order to limit the bias. Apart from the fact that this system does not guarantee a better evaluation of the manuscript, its main disadvantage is that the article is accessible without validation of the data collection and analysis throughout the entire process, which can be lengthy. Cost and funding of scientific journals: The cost of an article depends on charges that vary according to the conditions and places of production. Reviewers are volunteers. On the other hand, manuscript management, editing and distribution are carried out by professionals, which entail financial charges. Some of these costs are lower in low- and medium-resource countries, where economies of scale and higher benefits are possible. Conclusion: The limits of the historical model have led to the development of several business models of scientific journals, that are in constant evolution, especially the author pays model which promises open access to publications but impacts scientific production. However, the evaluation of scientific production is heterogeneous due to a limited pool of reviewers inadequately selected. Scientific publishing is looking for solutions to find a virtuous model that respects open science, open access to data and scientific integrity. The "Diamond open access" model, free of charge for both readers and authors with the guarantee of an irrevocable license to reproduce the content of the article provided that the original source is cited, perfectly fits.

[Assessment of a therapeutic protocol for the management of snakebite envenomations in Benin]. / Évaluation d'un protocole de traitement des envenimations ophidiennes au Bénin.

Introduction: Snakebite envenomation is a major public health issue in Sub-Saharan Africa (SSA). Antivenoms are the only etiological treatment. However, the dose recommended by the manufacturer (2 vials renewed every 2 hours in case of persistent bleeding) is usually not applied due to the high cost which is borne only by the patient. Based on clinical presentation, we evaluated the administration of a single vial on admission (instead of 2 vials), which corresponds to the therapeutic protocol used in current practice in most health centers in Benin and beyond in SSA. Renewal of antivenom followed manufacturer's recommendation. Material and method: The study took place in a first referral hospital in Tanguiéta, North Benin. All envenomed patients received a slow intravenous vial of Inoserp® Pan-Africa (IPA) upon arrival. A clinical assessment identical to that of inclusion was carried out 2, 4, 6, 12 and 24 hours later to assess the tolerance and efficacy of the IPA, as well as the need to readminister the antivenom. The occurrence, persistence or worsening of clinical hemorrhages or neurological disorders, the latter reflecting envenomation by elapids, systematically led to the injection of 2 or 4 vials of IPA, respectively. Signs of intolerance were sought before and after each administration of antivenom, then 2 weeks to 1 month after treatment, in order to estimate the incidence of adverse effects attributable to the antivenom. Efficacy of IPA was assessed by cessation of bleeding and/or normalization of whole blood coagulation test (WBCT) within 24 hours of initial administration. Results: The study took place from July 31 to October 31, 2019. We received 53 cases of snakebites of which 43 were included. The median age was 21 [IQR: 18-31] years and the sex ratio (M/F) was 1.5. Farmers were the majority (48%). The median time to admission was 1 [IQR: 0-2] day. On admission, 32 patients (74%) presented hemostasis disorders marked by bleeding and/or abnormal WBCT. None of the patients showed neurological symptoms. The median time to normalization of WBCT was 24 [IQR: 4-72] hours. The median time to stop bleeding was 6 [IQR: 4-12] hours. In 3 of the 11 patients whose bleeding had stopped at H2, a recurrence occurred within the following 24 hours. In addition, 3 patients presented with late bleeding 24 hours after admission. Two patients (5%) died as a result of envenomation. Discussion/conclusion: The simplified protocol represents a significant saving in the number of vials used, i.e. 1.8±0.4 vials per patient instead of the 2.4±0.2 which would have been necessary in these same patients treated according to the standard protocol (p = 2.6·10-4). However, in comparison with the results obtained during the previous clinical study, the cessation of bleeding is delayed, as is the normalization of the WBCT at the different follow-up times. In addition, the number of re-administrations of antivenom after H2 is higher in the light protocol than in the standard one, respectively 13 patients out of 43 treated versus 4 patients out of 59 (p = 0.006). There was no significant difference between the incidence of signs of early antivenom intolerance in this study compared to the previous one (16% and 11%, respectively; p = 0.79). This delay can put up to a third of patients at risk of complications. Despite its effectiveness and the antivenom savings made, it does not seem reasonable to recommend it.

Evaluating post-treatment Loa loa microfilarial densities to classify serious adverse events caused by ivermectin: a retrospective analysis.

BACKGROUND: The elimination of onchocerciasis requires increasing ivermectin treatment coverage in communities hypoendemic for onchocerciasis. In areas where loiasis is co-endemic, this approach is complicated by the risk of serious adverse events following treatment with ivermectin in individuals with a high Loa loa microfilarial density (MFD). We aimed to evaluate the extent to which the pre-treatment MFD can be inferred from post-treatment MFDs. METHODS: For this retrospective analysis, we used data from seven clinical or community trials (six were used for the main analysis and one for the secondary analysis) conducted in Cameroon, in which MFDs were measured both before and after (within 14 days) receiving a single dose of ivermectin (150-200 µg/kg bodyweight). The primary objective was to establish the receiver operating characteristic curves and the corresponding area under the curve statistics of MFD measured after treatment to classify pre-treatment MFD (MFDD0) according to common risk thresholds of serious adverse events. We assessed the performance of post-treatment MFD to accurately classify MFDD0 according to commonly used thresholds using bootstrap procedures. FINDINGS: 281 individuals with MFD measurements available before and 3-10 days after ivermectin treatment were enrolled. Our results show that an MFD of more than 3500 L loa microfilariae per mL of blood (mf per mL) 3 or 4 days after treatment indicates a 68·6% chance (positive predictive value) of an MFDD0 of more than 20 000 mf per mL. An MFD of more than 3500 mf per mL at day 5-10 corresponds to a 72·2% chance of having an MFDD0 of more than 20 000 mf per mL. Conversely, an MFD of less than 2500 microfilariae per mL at day 3-4 or day 5-10 corresponds to a probability of 92·3% or 92·8% (negative predictive value) of having MFDD0 of less than 20 000 mf per mL. An MFD less than 1500 mf per mL on days 3-4 after treatment was associated with a 78·3% probability of having an MFDD0 less than 8000 mf per mL; this probability increased to 89·6% on days 5-10 after treatment. INTERPRETATION: The MFD threshold of 1000 mf per mL within 1 month of treatment, which is commonly used to attribute the occurrence of a serious adverse event to ivermectin, should be revised. In this study, we present tables that can help to assess this attributability as part of mass or individual treatments. FUNDING: None.

Bothrops venom-induced hemostasis disorders in the rat: Between Scylla and Charybdis.

Hemostasis impairment represents the most threatening consequence of Viperidae envenoming, notably with Bothrops genus. In the French departments of America, B. atrox envenomation in French Guiana may lead to bleeding while B. lanceolatus envenomation in Martinique to thrombosis. Bleeding related to B. atrox envenomation is attributed to vascular damage mediated by venom metalloproteinases and blood uncoagulable state resulting from thrombocytopenia and consumptive coagulopathy. Thrombosis related to B. lanceolatus envenomation are poorly understood. We aimed to compare the effects of B. atrox and B. lanceolatus venoms in the rat to identify the determinants of the hemorrhagic versus thrombotic complications. Viscoelastometry (ROTEM), platelet count, plasma fibrinogen, thrombin generation assay, fibrinography, endothelial (von Willebrand factor, ADAMTS13 activity, ICAM-1, and soluble E-selectin), and inflammatory biomarkers (IL-1ß, IL-6, TNF-α, MCP-1, and PAI-1) were determined in blood samples obtained at H3, H6, and H24 after the subcutaneous venom versus saline injection. In comparison to the control, initial fibrinogen consumption was observed with the two venoms while thrombocytopenia and reduction in the clot amplitude only with B. atrox venom. Moreover, we showed an increase in thrombin generation at H3 with the two venoms, an increase in fibrin generation accompanied with hyperfibrinogenemia at H24 and an increase in inflammatory biomarkers with B. lanceolatus venom. No endothelial damage was found with the two venoms. To conclude, our data support two-sided hemostasis complications in Bothrops envenoming with an initial risk of hemorrhage related to platelet consumption and hypocoagulability followed by an increased risk of thrombosis promoted by the activated inflammatory response and rapid-onset fibrinogen restoration.

[Médecine Tropicale et Santé Internationale takes a stand against editorial predation]. / Médecine Tropicale et Santé Internationale s'engage contre la prédation éditoriale.

Warnings against predatory journals get stronger. Designed to capture manuscripts with the promise of rapid publication, the main aim of these journals is to charge abusive publication fees. Sometimes boasting imaginary impact factors, they are not indexed and offer no guarantee of visibility, accessibility or durability of the published article. Above all, they have no concern for the rigor and scientific integrity of the work they publish.

Bothrops atrox and Bothrops lanceolatus Venoms In Vitro Investigation: Composition, Procoagulant Effects, Co-Factor Dependency, and Correction Using Antivenoms.

Bothrops venoms are rich in enzymes acting on platelets and coagulation. This action is dependent on two major co-factors, i.e., calcium and phospholipids, while antivenoms variably neutralize venom-related coagulopathy effects. Our aims were (i) to describe the composition of B. atrox and B. lanceolatus venoms; (ii) to study their activity on the whole blood using rotational thromboelastometry (ROTEM); (iii) to evaluate the contribution of calcium and phospholipids in their activity; and (iv) to compare the effectiveness of four antivenoms (Bothrofav™, Inoserp™ South America, Antivipmyn™ TRI, and PoliVal-ICP™) on the procoagulant activity of these two venoms. Venom composition was comparable. Both venoms exhibited hypercoagulant effects. B. lanceolatus venom was completely dependent on calcium but less dependent on phospholipids than B. atrox venom to induce in vitro coagulation. The four antivenoms neutralized the procoagulant activity of the two venoms; however, with quantitative differences. Bothrofav™ was more effective against both venoms than the three other antivenoms. The relatively similar venom-induced effects in vitro were unexpected considering the opposite clinical manifestations resulting from envenomation (i.e., systemic bleeding with B. atrox and thrombosis with B. lanceolatus). In vivo studies are warranted to better understand the pathophysiology of systemic bleeding and thrombosis associated with Bothrops bites.

Real life condition evaluation of Inoserp PAN-AFRICA antivenom effectiveness in Cameroon.

BACKGROUND: Snakebites is a serious public health issue but remains a neglected tropical disease. Data on antivenom effectiveness are urgently needed in Africa. We assessed effectiveness of Inoserp PAN-AFRICA (IPA), the recommended antivenom available in Cameroon. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 447 patients presenting with snakebite in 14 health facilities across Cameroon. At presentation, cytotoxicity, coagulation troubles and neurotoxicity were graded. We administered two to four vials of antivenom to patients based on hemotoxic or neurotoxic signs. We renewed antivenom administration to patients with persistence of bleedings or neurotoxicity 2 hours after each injection. We defined early improvement as a reduction of the grade of envenomation symptoms 2 hours after first injection. Medium-term effectiveness was investigated looking at disappearance of symptoms during hospitalization. After hospital discharge, a home visit was planned to assess long-term outcomes. Between October 2019 and May 2021, we enrolled 447 (93.7%), including 72% from the savannah regions. The median [IQR] age was 25 [14-40]. Envenomation was diagnosed in 369 (82.6%) participants. The antivenom was administered to 356 patients (96.5%) of whom 256 (71.9%) received one administration. Among these patients, cytotoxic symptoms were observed in 336 (94.4%) participants, coagulation disorders in 234 (65.7%) participants and neurotoxicity in 23 (6.5%) participants. Two hours after the first administration of antivenom, we observed a decrease in coagulation disorders or neurotoxicity in 75.2% and 39.1% of patients, respectively. Complete cessation of bleedings and neurotoxicity occurred in 96% and 93% of patients within 24 hours, respectively. Sequelae have been observed in 9 (3%) patients at the home visit 15 days after hospital admission and 11 (3%) died including one before antivenom injection. CONCLUSIONS/SIGNIFICANCE: We confirmed good effectiveness of the IPA and highlighted the rapid improvement in bleeding or neurotoxicity after the first administration. Sequential administrations of low doses of antivenom, rigorously assessed at short intervals for an eventual renewal, can preserve patient safety and save antivenom. TRIAL REGISTRATION: NCT03326492.

A global core outcome measurement set for snakebite clinical trials.

Snakebite clinical trials have often used heterogeneous outcome measures and there is an urgent need for standardisation. A globally representative group of key stakeholders came together to reach consensus on a globally relevant set of core outcome measurements. Outcome domains and outcome measurement instruments were identified through searching the literature and a systematic review of snakebite clinical trials. Outcome domains were shortlisted by use of a questionnaire and consensus was reached among stakeholders and the patient group through facilitated discussions and voting. Five universal core outcome measures should be included in all future snakebite clinical trials-mortality, WHO disability assessment scale, patient-specific functional scale, acute allergic reaction by Brown criteria, and serum sickness by formal criteria. Additional syndrome-specific core outcome measures should be used depending on the biting species. This core outcome measurement set provides global standardisation, supports the priorities of patients and clinicians, enables meta-analysis, and is appropriate for use in low-income and middle-income settings.

[A global core outcome measurement set for snakebite clinical trials]. / Définition d'un jeu universel de critères de décision de base pour les essais cliniques sur les morsures de serpent.

Background: Snakebite clinical trials have often used heterogeneous outcome measures and there is an urgent need for standardisation. Method: A globally representative group of key stakeholders came together to reach consensus on a globally relevant set of core outcome measurements. Outcome domains and outcome measurement instruments were identified through searching the literature and a systematic review of snakebite clinical trials. Outcome domains were shortlisted by use of a questionnaire and consensus was reached among stakeholders and the patient group through facilitated discussions and voting. Results: Five universal core outcome measures should be included in all future snakebite clinical trials: mortality, WHO disability assessment scale, patient-specific functional scale, acute allergic reaction by Brown criteria, and serum sickness by formal criteria. Additional syndrome-specific core outcome measures should be used depending on the biting species. Conclusion: This core outcome measurement set provides global standardisation, supports the priorities of patients and clinicians, enables meta-analysis, and is appropriate for use in low-income and middle-income settings.

Computer-Aided Analysis of West Sub-Saharan Africa Snakes Venom towards the Design of Epitope-Based Poly-Specific Antivenoms.

Snakebite envenomation is a neglected tropical disease that causes over 100,000 deaths each year. The only effective treatment consists of antivenoms derived from animal sera, but these have been deemed with highly variable potency and are usually inaccessible and too costly for victims. The production of antivenoms by venom-independent techniques, such as the immunization with multi-epitope constructs, could circumvent those drawbacks. Herein, we present a knowledge-based pipeline to prioritize potential epitopes of therapeutic relevance from toxins of medically important snakes in West Sub-Saharan Africa. It is mainly based on sequence conservation and protein structural features. The ultimately selected 41 epitopes originate from 11 out of 16 snake species considered of highest medical importance in the region and 3 out of 10 of those considered as secondary medical importance. Echis ocellatus, responsible for the highest casualties in the area, would be covered by 12 different epitopes. Remarkably, this pipeline is versatile and customizable for the analysis of snake venom sequences from any other region of the world.