Snakebite envenoming: a neglected health crisis

Snakebite envenoming: a neglected health crisis

Every year 2 million or more people fall victim to snakebite envenoming, mostly in poor, rural communities of Africa, Asia and Latin America. Between 83,000—138,000 of them die, while hundreds of thousands more suffer debilitating long-term complications or disabilities. Although some antivenom medicines are highly effective when used promptly and appropriately, many snakebite victims get no treatment at all. Those who do may receive antivenoms which don’t work against the type of snake that bit them, or were not rigorously tested for safety and effectiveness. To mark International Snakebite Awareness Day on September 19th, the Collection linked below brings together recent MSF work on this highly neglected disease. Several articles and conference presentations help fill evidence gaps on the burden of disease and its impacts, or on treatment outcomes with specific antivenoms. Others examine how to tackle the formidable challenges of availability and affordability, the absence of regulatory oversight for making, testing and registering antivenoms, and the anemic R&D pipeline for new products—all of which impede access for patients to safe, effective treatment tailored to local snake species.

9 result(s)
Journal Article > CommentaryFull Text
Toxicon: X. 2023 February 26; Volume 18; 100152.
Dalhat MMPotet JMohammed AChotun NTesfahunei HA et al.
Toxicon: X. 2023 February 26; Volume 18; 100152.
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.
Journal Article > Meta-AnalysisFull Text
Lancet Global Health. 2023 February 1; Volume 11 (Issue 2); e296-e300.
Abouyannis MEsmail HHamaluba MNgama MMwangudzah H et al.
Lancet Global Health. 2023 February 1; Volume 11 (Issue 2); e296-e300.
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.
Journal Article > CommentaryFull Text
Toxicon: X. 2022 December 21; Volume 17; 100146.
Potet JSingh SNRitmeijer KKDSisay KAlcoba G et al.
Toxicon: X. 2022 December 21; Volume 17; 100146.
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.
Journal Article > CommentaryFull Text
PLoS Negl Trop Dis. 2022 November 17; Volume 16 (Issue 11); e0010897.
Gutiérrez JMBorri JGiles-Vernick TDuda RHabib AG et al.
PLoS Negl Trop Dis. 2022 November 17; Volume 16 (Issue 11); e0010897.
Journal Article > ReviewFull Text
Toxicon: X. 2022 March 1; Volume 13; 100089.
Alcoba GPotet JVatrinet RSingh SNNanclares C et al.
Toxicon: X. 2022 March 1; Volume 13; 100089.
Snakebite envenoming is a public health concern in many countries affected by humanitarian crises. Its magnitude was recognized internationally but associations between snakebite peaks and humanitarian crises were never clearly established or analysed. This scoping review searched any available evidence of this hypothesized association between snakebite types of crises, through PubMed/Medline by two researchers. The search also included hand searching, and reports from humanitarian organizations working in this area.

The scoping review yielded 41 results. None described a robust epidemiological link or evidence of causality. There is an evidence gap regarding our research question. Several publications however point or hint towards the occurrence of snakebite outbreaks during conflict, displacement, floods, and migration of impoverished agricultural workers. Non-systematic screening yielded another 11 publications (52 in total). We found Médecins Sans Frontières routine reports showing that 6469 patients were admitted in 2019 throughout its projects in 17 countries. The impact of snakebite was the highest in four countries particularly affected by humanitarian crises, South Sudan, Ethiopia, Central African Republic, and Yemen, with some hospitals receiving more than 1000 annual admissions. Time correlations with conflict and events are shown in Figures. We found no published epidemiological data formally showing any associations between humanitarian crises and snakebite incidence. However, the search publications showing peaks during crises, and monitoring curves in four countries point towards an increased risk during humanitarian crises.

We call for urgent population-based studies and surveillance. Stakeholders should consider upgrading snakebite care and antivenom supply during humanitarian crises in snakebite-endemic countries.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2022 February 9; Volume 16 (Issue 2); e0010148.
Steegemans IMSisay KNshimiyimana EGebrewold GPiening T et al.
PLoS Negl Trop Dis. 2022 February 9; Volume 16 (Issue 2); e0010148.
BACKGROUND
Millions of people are bitten by venomous snakes annually, causing high mortality and disability, but the true burden of this neglected health issue remains unknown. Since 2015, Médecins Sans Frontières has been treating snakebite patients in a field hospital in north-west Ethiopia. Due to the poor market situation for effective and safe antivenoms for Sub-Saharan Africa, preferred antivenom was not always available, forcing changes in choice of antivenom used. This study describes treatment outcomes and the effectiveness and safety of different antivenoms used.

METHODOLOGY/PRINCIPAL FINDINGS:
This retrospective observational study included 781 snakebite patients presenting at the field hospital between 2015 and 2019. Adjusted odds ratios, 95%-CI and p-values were used to compare the treatment outcome of patients treated with Fav-Afrique (n = 149), VacSera (n = 164), and EchiTAb-PLUS-ICP (n = 156) antivenom, and to identify the risk of adverse reactions for each antivenom. Whereas only incidental snakebite cases presented before 2015, after treatment was made available, cases rapidly increased to 1,431 in 2019. Envenomation was mainly attributed to North East African saw-scaled viper (Echis pyramidum) and puff adder (Bitis arietans). Patients treated with VacSera antivenom showed lower chance of uncomplicated treatment outcome (74.4%) compared to Fav-Afrique (93.2%) and EchiTAb-PLUS-ICP (90.4%). VacSera and EchiTAb-PLUS-ICP were associated with 16- and 6-fold adjusted odds of treatment reaction compared to Fav-Afrique, respectively, and VacSera was weakly associated with higher odds of death.

CONCLUSIONS/SIGNIFICANCE
Snakebite frequency is grossly underreported unless treatment options are available. Although EchiTAb-PLUS-ICP showed favorable outcomes in this retrospective analysis, prospective randomized trials are needed to evaluate the effectiveness and safety of the most promising antivenoms for Sub-Saharan Africa. Structural investment in sustained production and supply of antivenom is urgently needed.
Journal Article > ReviewFull Text
Toxicon: X. 2021 October 26; Volume 12; 100086.
Potet JBeran DRay NAlcoba GHabib AG et al.
Toxicon: X. 2021 October 26; Volume 12; 100086.
Access to safe, effective, quality-assured antivenom products that are tailored to endemic venomous snake species is a crucial component of recent coordinated efforts to reduce the global burden of snakebite envenoming. Multiple access barriers may affect the journey of antivenoms from manufacturers to the bedsides of patients. Our review describes the antivenom ecosystem at different levels and identifies solutions to overcome these challenges. At the global level, there is insufficient manufacturing output to meet clinical needs, notably for antivenoms intended for use in regions with a scarcity of producers. At national level, variable funding and deficient regulation of certain antivenom markets can lead to the procurement of substandard antivenom. This is particularly true when producers fail to seek registration of their products in the countries where they should be used, or where weak assessment frameworks allow registration without local clinical evaluation. Out-of-pocket expenses by snakebite victims are often the main source of financing antivenoms, which results in the underuse or under-dosing of antivenoms, and a preference for low-cost products regardless of efficacy. In resource-constrained rural areas, where the majority of victims are bitten, supply of antivenom in peripheral health facilities is often unreliable. Misconceptions about treatment of snakebite envenoming are common, further reducing demand for antivenom and exacerbating delays in reaching facilities equipped for antivenom use. Multifaceted interventions are needed to improve antivenom access in resource-limited settings. Particular attention should be paid to the comprehensive list of actions proposed within the WHO Strategy for Prevention and Control of Snakebite Envenoming.
Journal Article > CommentaryFull Text
BMJ Glob Health. 2021 October 25; Volume 6 (Issue 10); e006913.
Martins DRibeiro IPotet J
BMJ Glob Health. 2021 October 25; Volume 6 (Issue 10); e006913.
SUMMARY POINTS

• Despite inherent differences, Snakebite Envenoming and COVID-19 have much in common in terms of research and development (R&D) challenges and opportunities.
• Both crises require a diversified portfolio of R&D solutions, ranging from diagnostics to treatments, that can effectively work and be accessible in different resource settings.
• Collaborative clinical research and streamlined regulatory pathways are critical to accelerate these candidates in the R&D pipeline.
• Transformative progress is possible with a concerted approach that aligns strong political will, coordinated financing and the needs of the most marginalised communities.
Conference Material > Abstract
Karl F
Epicentre Scientific Day Paris 2021. 2021 June 10
BACKGROUND
While 2.5 million envenomings and 130,000 deaths occur globally due to snakebites, with 1 million envenomings and 30,000 deaths in sub-Saharan Africa, the accessibility of antivenom for treatment of snakebites remain limited. The Inoserp® Pan-Africa antivenom is being used in many African countries including Cameroon but there is few data on its efficacy or tolerance in those settings. We therefore aim to evaluate the tolerance and efficacy of the Inoserp® Pan-Africa antivenom (AVS) in Cameroon.

METHODS
We performed a Phase IV clinical trial and included participants 5 years and above with snakebites in 14 healthcare centers across 6 of the 10 regions of Cameroon. Participants with envenomation were treated with Inoserp AVS and followed-up for 3 days in the hospital and 15 more days at home. The main study endpoints were complete follow-up to day 15, occurrence of adverse events, including disability or death.

RESULTS
Between October 15, 2019 and April 30, 2021, we included 427 participants with snakebites. Echis ocellatus (43.3%) was the most incriminated. Most frequent signs at admission were pain and edema with 90.9% (388/427) and 75.2% (321/427) respectively. We administered AVS to 81.3% (347/427) of patients with an average dose of 2 doses of AVS. Coagulation disorders was present in 50.4% (215/427) of the participants. We reported 12 deaths (2.7%); none were imputed to the administration of AVS. According to preliminary analysis necessitating confirmation, we observed at least one mild or moderate adverse event in 75 of 347 patients (21.6%), including tachypnea, tachycardia and bradycardia.

CONCLUSIONS
Snakebites are still an important neglected problem. Treatment with the Inoserp® Pan-Africa AVS appeared to be well tolerated in the Cameroonian patients and ongoing analysis will help to better assess its effectiveness.

KEY MESSAGES: Snakebites are neglected and their management is most at times inappropriate. We found the Inoserp® Pan-Africa antivenom to be well tolerated in the Cameroonian population.

This abstract is not to be quoted for publication.