Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial.

BACKGROUND: This study aimed to determine whether paromomycin plus miltefosine (PM/MF) is noninferior to sodium stibogluconate plus paromomycin (SSG/PM) for treatment of primary visceral leishmaniasis in eastern Africa. METHODS: An open-label, phase 3, randomized, controlled trial was conducted in adult and pediatric patients at 7 sites in eastern Africa. Patients were randomly assigned to either 20 mg/kg paromomycin plus allometric dose of miltefosine (14 days), or 20 mg/kg sodium stibogluconate plus 15 mg/kg paromomycin (17 days). The primary endpoint was definitive cure after 6 months. RESULTS: Of 439 randomized patients, 424 completed the trial. Definitive cure at 6 months was 91.2% (155 of 170) and 91.8% (156 of 170) in the PM/MF and SSG/PM arms in primary efficacy modified intention-to-treat analysis (difference, 0.6%; 97.5% confidence interval [CI], -6.2 to 7.4), narrowly missing the noninferiority margin of 7%. In the per-protocol analysis, efficacy was 92% (149 of 162) and 91.7% (155 of 169) in the PM/MF and SSG/PM arms (difference, -0.3%; 97.5% CI, -7.0 to 6.5), demonstrating noninferiority. Treatments were well tolerated. Four of 18 serious adverse events were study drug-related, and 1 death was SSG-related. Allometric dosing ensured similar MF exposure in children (<12 years) and adults. CONCLUSIONS: PM/MF and SSG/PM efficacies were similar, and adverse drug reactions were as expected given the drugs safety profiles. With 1 less injection each day, reduced treatment duration, and no risk of SSG-associated life-threatening cardiotoxicity, PM/MF is a more patient-friendly alternative for children and adults with primary visceral leishmaniasis in eastern Africa. CLINICAL TRIALS REGISTRATION: NCT03129646.

[Traveler's consultations in time of pandemic COVID-19: changing practices and sentinel role ?] / Consultation des voyageurs en temps de pandémie de Covid-19: évolution des pratiques et rôle sentinelle ?

What is the status of travel medicine in the context of the COVID-19 pandemic? This article describes the evolution of travel medicine consultations at the University Hospital of Geneva with the introduction of pre-travel screening for the SARS-CoV-2 virus. 9141 travelers were screened between August 2020 and January 2021 for various destinations, one third of which were intra-European. The various international restrictions led to the creation of thirteen separate medical certificates and a list of requirements for 150 countries updated weekly. A significant increase in positivity (up to 5%) in the asymptomatic traveler was associated with the months of October and November 2020 and with certain destinations. This rate of positivity in the asymptomatic traveler population could be a sentinel indicator of viral transmission in the community.

Quel est l'état des lieux de la médecine des voyages en temps de pandémie de Covid-19? Cet article décrit l'évolution des consultations de médecine des voyages aux HUG avec l'introduction du dépistage prévoyage du SARS-CoV-2. 9141 voyageurs ont été dépistés entre août 2020 et janvier 2021 pour des destinations variées, dont un tiers intra-européennes. Les différentes restrictions internationales ont induit la création de treize attestations médicales distinctes et d'une liste des exigences pour 150 pays mise à jour chaque semaine. Une augmentation significative de la positivité (jusqu'à 5 %) chez le voyageur asymptomatique a été associée aux mois d'octobre et novembre 2020 et à certaines destinations. Ce taux de positivité dans la population asymptomatique de voyageurs pourrait être un indicateur sentinelle de la transmission virale dans la communauté.

[Sea bathing dangers: marine envenoming, trauma, and infections]. / Envenimations, infections et traumatismes en mer.

Sea bathing is often a priority activity for travelers, with widely recognized health benefits. The dangers, in contrast, are underestimated, especially in tropical seas. We describe the scope of marine envenoming, trauma, and infections, representing 1-3 % of tropical and travel medicine consultations in the literature. Our review includes the eco-epidemiology, clinical approach, and prevention of envenoming by invertebrates (jellyfish, anemone, sea-urchin, starfish, octopus, sea cone) and some vertebrates (stingrays, stone fish, snakes). We include penetrating trauma (by stingray, stonefish, sea urchin, coral) and infections (mycobacteria, marine bacteria). Eating-related dangers (ciguatera, fugu, parasites) are not described here. We also present antidotes, antivenoms, and first-aid.

Les baignades en mer aux bienfaits reconnus font souvent partie des activités prioritaires des voyageurs. Mais les dangers, notamment en mer tropicale, sont sous-estimés. Nous décrivons l'éventail des envenimations, traumatismes et infections marins, soit 1 à 3 % des consultations de médecine tropicale et des voyages dans la littérature. Notre revue inclut l'éco-épidémiologie, l'approche clinique et la prévention des envenimations par des invertébrés (méduses, anémones, oursins, étoiles de mer, poulpes et cônes) et certains vertébrés (raies, poissons-pierre, serpents). Elle inclut les traumatismes pénétrants (raies, poissons-pierre) et les infections par contact (mycobactéries, bactéries marines). Les dangers alimentaires (ciguatera, fugu, parasites) ne sont pas décrits ici. Les antidotes, antivenins et premiers secours sont également présentés.

Vulnerability to snakebite envenoming: a global mapping of hotspots.

BACKGROUND: Snakebite envenoming is a frequently overlooked cause of mortality and morbidity. Data for snake ecology and existing snakebite interventions are scarce, limiting accurate burden estimation initiatives. Low global awareness stunts new interventions, adequate health resources, and available health care. Therefore, we aimed to synthesise currently available data to identify the most vulnerable populations at risk of snakebite, and where additional data to manage this global problem are needed. METHODS: We assembled a list of snake species using WHO guidelines. Where relevant, we obtained expert opinion range (EOR) maps from WHO or the Clinical Toxinology Resources. We also obtained occurrence data for each snake species from a variety of websites, such as VertNet and iNaturalist, using the spocc R package (version 0.7.0). We removed duplicate occurrence data and categorised snakes into three groups: group A (no available EOR map or species occurrence records), group B (EOR map but <5 species occurrence records), and group C (EOR map and ≥5 species occurrence records). For group C species, we did a multivariate environmental similarity analysis using the 2008 WHO EOR maps and newly available evidence. Using these data and the EOR maps, we produced contemporary range maps for medically important venomous snake species at a 5 × 5 km resolution. We subsequently triangulated these data with three health system metrics (antivenom availability, accessibility to urban centres, and the Healthcare Access and Quality [HAQ] Index) to identify the populations most vulnerable to snakebite morbidity and mortality. FINDINGS: We provide a map showing the ranges of 278 snake species globally. Although about 6·85 billion people worldwide live within range of areas inhabited by snakes, about 146·70 million live within remote areas lacking quality health-care provisioning. Comparing opposite ends of the HAQ Index, 272·91 million individuals (65·25%) of the population within the lowest decile are at risk of exposure to any snake for which no effective therapy exists compared with 519·46 million individuals (27·79%) within the highest HAQ Index decile, showing a disproportionate coverage in reported antivenom availability. Antivenoms were available for 119 (43%) of 278 snake species evaluated by WHO, while globally 750·19 million (10·95%) of those living within snake ranges live more than 1 h from population centres. In total, we identify about 92·66 million people living within these vulnerable geographies, including many sub-Saharan countries, Indonesia, and other parts of southeast Asia. INTERPRETATION: Identifying exact populations vulnerable to the most severe outcomes of snakebite envenoming at a subnational level is important for prioritising new data collection and collation, reinforcing envenoming treatment, existing health-care systems, and deploying currently available and future interventions. These maps can guide future research efforts on snakebite envenoming from both ecological and public health perspectives and better target future estimates of the burden of this neglected tropical disease. FUNDING: Bill & Melinda Gates Foundation.

Single-dose oral ciprofloxacin prophylaxis as a response to a meningococcal meningitis epidemic in the African meningitis belt: A 3-arm, open-label, cluster-randomized trial.

BACKGROUND: Antibiotic prophylaxis for contacts of meningitis cases is not recommended during outbreaks in the African meningitis belt. We assessed the effectiveness of single-dose oral ciprofloxacin administered to household contacts and in village-wide distributions on the overall attack rate (AR) in an outbreak of meningococcal meningitis. METHODS AND FINDINGS: In this 3-arm, open-label, cluster-randomized trial during a meningococcal meningitis outbreak in Madarounfa District, Niger, villages notifying a suspected case were randomly assigned (1:1:1) to standard care (the control arm), single-dose oral ciprofloxacin for household contacts within 24 hours of case notification, or village-wide distribution of ciprofloxacin within 72 hours of first case notification. The primary outcome was the overall AR of suspected meningitis after inclusion. A random sample of 20 participating villages was enrolled to document any changes in fecal carriage prevalence of ciprofloxacin-resistant and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae before and after the intervention. Between April 22 and May 18, 2017, 49 villages were included: 17 to the control arm, 17 to household prophylaxis, and 15 to village-wide prophylaxis. A total of 248 cases were notified in the study after the index cases. The AR was 451 per 100,000 persons in the control arm, 386 per 100,000 persons in the household prophylaxis arm (t test versus control p = 0.68), and 190 per 100,000 persons in the village-wide prophylaxis arm (t test versus control p = 0.032). The adjusted AR ratio between the household prophylaxis arm and the control arm was 0.94 (95% CI 0.52-1.73, p = 0.85), and the adjusted AR ratio between the village-wide prophylaxis arm and the control arm was 0.40 (95% CI 0.19‒0.87, p = 0.022). No adverse events were notified. Baseline carriage prevalence of ciprofloxacin-resistant Enterobacteriaceae was 95% and of ESBL-producing Enterobacteriaceae was >90%, and did not change post-intervention. One limitation of the study was the small number of cerebrospinal fluid samples sent for confirmatory testing. CONCLUSIONS: Village-wide distribution of single-dose oral ciprofloxacin within 72 hours of case notification reduced overall meningitis AR. Distributions of ciprofloxacin could be an effective tool in future meningitis outbreak responses, but further studies investigating length of protection, effectiveness in urban settings, and potential impact on antimicrobial resistance patterns should be carried out. TRIAL REGISTRATION: ClinicalTrials.gov NCT02724046.

A three-step diagnosis of pediatric pneumonia at the emergency department using clinical predictors, C-reactive protein, and pneumococcal PCR.

Recommendations for the management of community-acquired pneumonia (CAP) advocate that, in the absence of the clinical and laboratory findings typical of bacterial CAP, antibiotics are not required. However, the true value of the clinical and laboratory predictors of pediatric CAP still needs to be assessed. This prospective cohort study in three emergency departments enrolled 142 children with radiological pneumonia. Pneumonia with lung consolidation was the primary endpoint; complicated pneumonia (bacteremia, empyema, or pleural effusion) was the secondary endpoint. We showed that three clinical signs (unilateral hypoventilation, grunting, and absence of wheezing), elevated procalcitonin (PCT), C-reactive protein (CRP), negative nasopharyngeal viral PCR, or positive blood pneumococcal PCR (P-PCR) were significantly associated with both pneumonia with consolidation and complicated pneumonia. Children with negative clinical signs and low CRP values had a low probability of having pneumonia with consolidation (13%) or complicated pneumonia (6%). Associating the three clinical signs, CRP >80 mg/L and a positive P-PCR ruled in the diagnosis of complicated pneumonia with a positive predictive value of 75%. CONCLUSION: A model incorporating clinical signs and laboratory markers can effectively assess the risk of having pneumonia. Children with negative clinical signs and low CRP are at a low risk of having pneumonia. For children with positive clinical signs and high CRP, a positive blood pneumococcal PCR can more accurately confirm the diagnosis of pneumonia. What is Known: • Distinguishing between bacterial and viral pneumonia in children is challenging. • Reducing the inappropriate use of antibiotics is a priority. What is New: • Children with negative clinical signs and low C-reactive protein (CRP) values have a low probability of having pneumonia. • Children with high CRP values can be tested using a pneumococcal PCR to rule in the diagnosis of pneumonia with a high positive predictive value.

Swiss and tropical snakebites: the clinical management. / Morsures de serpents suisses et tropicaux : prise en charge.

With increasing trips to tropical areas, as well as a high number of venomous snake holders in the country, the frequency of snake bites is likely to increase. Even if in 50 % of cases, the bites do not lead to clinical envenoming, rapid and effective management is essential to successful treatment, which includes supply with the polyvalent or specific antivenom and recognition of the signs and symptoms justifying its administration. We will deal here mainly with local and tropical snake envenoming that Swiss practitioners could encounter in their offices or the emergency rooms and propose scenarios according to the syndromes.

Avec l'augmentation des voyages dans les zones tropicales, de même que du nombre de détenteurs de serpents venimeux à domicile, la fréquence des morsures de serpents risque d'augmenter. Même si dans 50 % des cas les morsures ne conduisent pas à une envenimation clinique, une prise en charge rapide et ciblée améliore les chances de succès thérapeutique. Ceci suppose un approvisionnement avec l'antivenin polyvalent ou spécifique et la reconnaissance des signes et des symptômes justifiant son administration. Nous traiterons ici essentiellement des envenimations par des serpents locaux ou tropicaux que le praticien suisse pourrait rencontrer au cabinet ou aux urgences en nous basant sur quelques vignettes et en proposant des scénarios en fonction des syndromes.

Partnerships in global health and collaborative governance: lessons learnt from the Division of Tropical and Humanitarian Medicine at the Geneva University Hospitals.

BACKGROUND: In 2007 the "Crisp Report" on international partnerships increased interest in Northern countries on the way their links with Southern partners operated. Since its establishment in 2007 the Division of Tropical and Humanitarian Medicine at the Geneva University Hospitals has developed a variety of partnerships. Frameworks to assess these partnerships are needed and recent attention in the field of public management on collaborative governance may provide a useful approach for analyzing international collaborations. METHODS: Projects of the Division of Tropical and Humanitarian Medicine were analyzed by collaborators within the Division using the model proposed by Emerson and colleagues for collaborative governance, which comprises different components that assess the collaborative process. RESULTS: International projects within the Division of Tropical and Humanitarian Medicine can be divided into four categories: Human resource development; Humanitarian response; Neglected Tropical Diseases and Noncommunicable diseases. For each of these projects there was a clear leader from the Division of Tropical and Humanitarian Medicine as well as a local counterpart. These individuals were seen as leaders both due to their role in establishing the collaboration as well as their technical expertise. Across these projects the actual partners vary greatly. This diversity means a wide range of contributions to the collaboration, but also complexity in managing different interests. A common definition of the collaborative aims in each of the projects is both a formal and informal process. Legal, financial and administrative aspects of the collaboration are the formal elements. These can be a challenge based on different administrative requirements. Friendship is part of the informal aspects and helps contribute to a relationship that is not exclusively professional. CONCLUSION: Using collaborative governance allows the complexity of managing partnerships to be presented. The framework used highlights the process of establishing collaborations, which is an element often negated by other more traditional models used in international partnerships. Applying the framework to the projects of the Division of Tropical and Humanitarian Medicine highlights the importance of shared values and interests, credibility of partners, formal and informal methods of management as well as friendship.

Sodium stibogluconate and paromomycin for treating visceral leishmaniasis under routine conditions in eastern Sudan.

OBJECTIVES: Among patients with primary and relapse visceral leishmaniasis (VL) in eastern Sudan, we determined the proportion eligible for treatment with sodium stibogluconate and paromomycin (SSG/PM) and, of these, their demographic and clinical characteristics; initial treatment outcomes including adverse side effects requiring treatment discontinuation; treatment outcomes by 6 months; and risk factors associated with initial (slow responders) and late treatment failure (relapses and post-kala-azar dermal leishmaniasis, PKDL). METHODS: A retrospective cohort study in Tabarak Allah Hospital, Gedaref Province, eastern Sudan, from July 2011 to January 2014. RESULTS: Of 1252 individuals diagnosed with VL (1151 primary and 101 relapses), 65% were eligible for SSG/PM including 83% children, almost half of them malnourished and anaemic. About 4% of individuals discontinued treatment due to side effects; 0.7% died during treatment. Initial cure was achieved in 93% of 774 primary cases and 77% of 35 relapse cases (P < 0.001). Among the 809 patients eligible for SSG/PM, 218 (27%) were lost to follow-up. Outcomes by six months among the 591 patients with available follow-up data were: definitive cure (n = 506; 86%), relapse (n = 38; 6%), treatment discontinuation (n = 33; 6%), PKDL (n = 7; 1%) and death (n = 7; 1%). Among those completing a full course of SSG/PM, relapses and under-fives were at significantly higher risk of early and late treatment failure, respectively. CONCLUSION: Whether SSG/PM as a first-line regimen is an undeniable progress compared to SSG monotherapy, it excluded a considerable proportion of VL patients due to drug safety concerns. We call for accelerated development of new drugs and treatment regimens to improve VL treatment in Sudan.

Proadrenomedullin and copeptin in pediatric pneumonia: a prospective diagnostic accuracy study.

BACKGROUND: Community-acquired-pneumonia is the leading cause of child mortality worldwide. Very few studies have explored the predictive value of Proadrenomedullin and Copeptin in pediatric severe pneumonia and bacteremia. METHODS: Proadrenomedullin and Copeptin were assessed as predictors for complicated community-acquired pneumonia (bacteremia, empyema) in 88 children aged 0 to 16 years presenting to the pediatric emergency department, using B.R.A.H.M.S. Kryptor Compact pro-ADM and Copeptin with the TRACE technology (time-resolved amplified cryptase emission). STARD standard reporting was used. RESULTS: A complicated community-acquired pneumonia was found in 11 out of 88 children (12.5 %). Proadrenomedullin median values increased more than twofold, in complicated vs. uncomplicated (0.18 vs. 0.08 nmol/L, p = 0.039), and fivefold in bacteremic vs. non-bacteremic pneumonia (0.40 vs. 0.08 nmol/L, p = 0.02). Proadrenomedullin > 0.16 nmol/L showed 100 % sensitivity (95 % CI 39.8 - 100.0) and 70 % (95 % CI 58.7 - 79.7) specificity for bacteremia. Copeptin showed no added-value. CONCLUSIONS: Proadrenomedullin seems a reliable and available predictor for complicated CAP, and could therefore help the physician with the decision to hospitalize, and choose the antibiotics administration route. Larger studies are needed.

Virologic testing in bronchiolitis: does it change management decisions and predict outcomes?

UNLABELLED: The aim of this study was to evaluate the clinical, therapeutic, laboratory, and radiological differences between respiratory syncytial virus (RSV) and non-RSV bronchiolitis in order to assess if the prior knowledge of viral etiology changed management decisions and would be able to predict outcomes. Medical charts of children <1 year admitted to the emergency department with bronchiolitis during two RSV seasons (2010-2012) were reviewed. We analyzed 221 episodes of bronchiolitis. The percentage of exams performed (95 % confidence interval (CI) 0.74-2.52), abnormal laboratory and radiological findings (95 % CI 0.53-16.89) did not differ between groups. RSV bronchiolitis had a more severe clinical course. However, virologic testing for RSV had low specificity in identifying at-risk patients for hospitalization, longer hospital length of stay, and need of oxygen therapy and nasogastric tube (44, 40, 42, and 35 %, respectively), and while statistically significant, the positive likelihood ratios were only slightly greater than 1. CONCLUSION: Although RSV bronchiolitis has a more severe clinical course, virologic testing does not help in management decisions, and at an individual level, as a performance test, it seems insufficient to precisely predict outcomes.

Neglected etiologies of prolonged febrile illnesses in tropical and subtropical regions: A systematic review.

BACKGROUND: Febrile illnesses that persist despite initial treatment are common clinical challenges in (sub)tropical low-resource settings. Our aim is to review infectious etiologies of "prolonged fevers" (persistent febrile illnesses, PFI) and to quantify relative contributions of selected neglected target diseases with limited diagnostic options, often overlooked, causing inadequate antibiotic prescriptions, or requiring prolonged and potentially toxic treatments. METHODS: We performed a systematic review of articles addressing the infectious etiologies of PFI in adults and children in sub-/tropical low- and middle-income countries (LMICs) using the PRISMA guidelines. A list of target diseases, including neglected parasites and zoonotic bacteria (e.g., Leishmania and Brucella), were identified by infectious diseases and tropical medicine specialists and prioritized in the search. Malaria and tuberculosis (TB) were not included as target diseases due to well-established epidemiology and diagnostic options. Four co-investigators independently extracted data from the identified articles while assessing for risk of bias. RESULTS: 196 articles from 52 countries were included, 117 from Africa (33 countries), 71 from Asia (16 countries), and 8 from Central and -South America (3 countries). Target diseases were reported as the cause of PFI in almost half of the articles, most frequently rickettsioses (including scrub typhus), relapsing fever borreliosis (RF-borreliosis), brucellosis, enteric fever, leptospirosis, Q fever and leishmaniasis. Among those, RF-borreliosis was by far the most frequently reported disease in Africa, particularly in Eastern Africa. Rickettsioses (including scrub typhus) were often described in both Africa and Asia. Leishmaniasis, toxoplasmosis and amoebiasis were the most frequent parasitic etiologies. Non-target diseases and non-tropical organisms (Streptococcus pneumoniae, Escherichia coli, and non-typhoidal Salmonella spp) were documented in a fifth of articles. CONCLUSIONS: Clinicians faced with PFI in sub-/tropical LMICs should consider a wide differential diagnosis including enteric fever and zoonotic bacterial diseases (e.g., rickettsiosis, RF-borreliosis and brucellosis), or parasite infections (e.g., leishmaniasis) depending on geography and syndromes. In the absence of adequate diagnostic capacity, a trial of antibiotics targeting relevant intra-cellular bacteria, such as doxycycline or azithromycin, may be considered.

Correction: Treatment outcomes among snakebite patients in north-west Ethiopia-A retrospective analysis.

[This corrects the article DOI: 10.1371/journal.pntd.0010148.].

Nasopharyngeal carriage of individual Streptococcus pneumoniae serotypes during pediatric radiologically confirmed community acquired pneumonia following PCV7 introduction in Switzerland.

BACKGROUND: Community-acquired pneumonia (CAP) is a serious cause of morbidity among children in developed countries. The real impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal pneumonia is difficult to assess accurately. METHODS: Children aged ≤16 years with clinical and radiological pneumonia were enrolled in a multicenter prospective study. Children aged ≤16 years admitted for a minor elective surgery was recruited as controls. Nasopharyngeal samples for PCR serotyping of S. pneumoniae were obtained in both groups. Informations on age, gender, PCV7 vaccination status, day care/school attendance, siblings, tobacco exposure were collected. RESULTS: In children with CAP (n=236), 54% of the nasopharyngeal swabs were PCR-positive for S. pneumoniae compared to 32% in controls (n=105) (p=0.003). Serotype 19A was the most common pneumococcal serotype carried in children with CAP (13%) and in controls (15%). Most common serotypes were non-vaccine types (39.4% for CAP and 47.1% for controls) and serotypes included only in PCV13 (32.3% for CAP and 23.5% for controls). There was no significant difference in vaccine serotype distribution between the two groups. In fully vaccinated children with CAP, the proportion of serotypes carried only in PCV13 was higher (51.4%) than in partially vaccinated or non vaccinated children (27.6% and 28.6% respectively, p=0.037). CONCLUSIONS: Two to 4 years following introduction of PCV7, predominant S. pneumoniae serotypes carried in children with CAP were non PCV7 serotypes, and the 6 new serotypes included in PCV13 accounted for 51.4% of carried serotypes in fully vaccinated children.

Vulnerability to snakebite envenoming and access to healthcare in the Terai region of Nepal: a geospatial analysis.

Background: Snakebite envenoming is a neglected tropical disease that mainly affects poor populations in rural areas. In hyperendemic regions, prevention could partially reduce the constant risk, but the population still needs timely access to adequate treatment. In line with WHO's snakebite roadmap, we aim to understand snakebite vulnerability through modelling of risk and access to treatment, and propose plausible solutions to optimise resource allocation. Methods: We combined snakebite-risk distribution rasters with travel-time accessibility analyses for the Terai region of Nepal, considering three vehicle types, two seasons, two snakebite syndromes, and uncertainty intervals. We proposed localised and generalised optimisation scenarios to improve snakebite treatment coverage for the population, focusing on the neurotoxic syndrome. Findings: In the Terai, the neurotoxic syndrome is the main factor leading to high snakebite vulnerability. For the most common scenario of season, syndrome, and transport, an estimated 2.07 (15.3%) million rural people fall into the high vulnerability class. This ranges between 0.3 (2.29%) and 6.8 (50.43%) million people when considering the most optimistic and most pessimistic scenarios, respectively. If all health facilities treating snakebite envenoming could optimally treat both syndromes, treatment coverage of the rural population could increase from 65.93% to 93.74%, representing a difference of >3.8 million people. Interpretation: This study is the first high-resolution analysis of snakebite vulnerability, accounting for uncertainties in both risk and travel speed. The results can help identify populations highly vulnerable to snakebite envenoming, optimise resource allocation, and support WHO's snakebite roadmap efforts. Funding: Swiss National Science Foundation.

Snakebite envenoming at MSF: A decade of clinical challenges and antivenom access issues.

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.

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.

An artificial intelligence model to identify snakes from across the world: Opportunities and challenges for global health and herpetology.

BACKGROUND: Snakebite envenoming is a neglected tropical disease that kills an estimated 81,000 to 138,000 people and disables another 400,000 globally every year. The World Health Organization aims to halve this burden by 2030. To achieve this ambitious goal, we need to close the data gap in snake ecology and snakebite epidemiology and give healthcare providers up-to-date knowledge and access to better diagnostic tools. An essential first step is to improve the capacity to identify biting snakes taxonomically. The existence of AI-based identification tools for other animals offers an innovative opportunity to apply machine learning to snake identification and snakebite envenoming, a life-threatening situation. METHODOLOGY: We developed an AI model based on Vision Transformer, a recent neural network architecture, and a comprehensive snake photo dataset of 386,006 training photos covering 198 venomous and 574 non-venomous snake species from 188 countries. We gathered photos from online biodiversity platforms (iNaturalist and HerpMapper) and a photo-sharing site (Flickr). PRINCIPAL FINDINGS: The model macro-averaged F1 score, which reflects the species-wise performance as averaging performance for each species, is 92.2%. The accuracy on a species and genus level is 96.0% and 99.0%, respectively. The average accuracy per country is 94.2%. The model accurately classifies selected venomous and non-venomous lookalike species from Southeast Asia and sub-Saharan Africa. CONCLUSIONS: To our knowledge, this model's taxonomic and geographic coverage and performance are unprecedented. This model could provide high-speed and low-cost snake identification to support snakebite victims and healthcare providers in low-resource settings, as well as zoologists, conservationists, and nature lovers from across the world.