Introduction
Setting the scene with snakes and snakebites as an example
The context of snakebite envenoming and other forms of envenoming and poisoning
- Snakebite envenoming is a neglected tropical disease, as are the envenoming and poisoning caused by a wide range of other terrestrial and aquatic animals.
- When considering patients affected by envenoming or poisoning from aquatic or terrestrial animals, it is equally appropriate to describe them as 'neglected', especially if they live in socioeconomically disadvantaged parts of the world with dysfunctional healthcare systems.
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The right to live without physical or mental harm, and the protection of the biosphere — to which both humans and venomous and poisonous animals belong — are under increasing threat, and are increasingly coming into conflict with each other. The people responsible for these alarming developments are not usually among those most immediately affected by their consequences, such as climate change, uncontrolled urbanisation, biosphere degradation and species extinction — at least not until it may be too late.
The 'neglect' has various levels
- There are gaps in our knowledge of venomous and poisonous animals and their behaviour. We still need to improve our understanding of the pathophysiology of venoms and poisons in humans, and of the therapeutics that counteract their effects.
- Interest in investing in the development of both new (e.g. “small molecules”) and established therapeutics (e.g. antivenoms) remains too low.
- There is insufficient production and access to therapeutics of an appropriate standard (GMP), such as antivenoms (the specific therapy for envenoming) and antidotes (for poisoning).
- The rapidly changing overlaps between the living spaces of humans, life stock and venomous and poisonous animals require greater attention, regulation and investment (e.g. due to changes in land use and the need to ensure safety at work and at home).
- The key to providing treatment and saving lives is functional health services with trained personnel, sustained availability of equipment and materials, and access to financing.
Framework of the VAPAGuide strategy
emergency assessment & supportive emergency treatment
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Collecting key information about an illness or injury in a standardised way using the SAMPLE approach, such as exploring acute signs and symptoms and asking about allergies and medications.
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Employing the ABCDE approach applicable to all medical emergencies. This includes clearing blocked airways, providing respiratory support if a patient stops breathing and administering cardiovascular treatment if circulation or heart function fails, etc..
Comprehensive ABCDE approach
ICRC Basic Emergency Care: approach to the acutely ill and injured
Specific therapeutics
- Antivenoms and antidotes are essential for treating envenoming and poisoning. They are particularly indispensable when the effects of venoms and poisons cannot be managed at all, or not effectively, with supportive therapy alone (e.g. unclottable blood and bleeding in snakebite envenoming).
Some effects of venoms and poisons can still be managed with supportive treatment if no antivenom is available or fails (e.g. respiratory failure due to venom-induced disabeling of the neuromuscular junction). - Specific therapeutics' require identification of the culprit.
In most cases of envenoming, the culprit has not been seen at all, has only been seen vaguely, has not been reliably identified, or has not been perceived as a threat.
In cases where only monospecific antivenoms are available, selecting the correct antivenom can be challenging. A high degree of certainty must be achieved in identifying the culprit using indirect evidence.
If polyspecific antivenoms covering the main culprits in a given region are available, it is less demanding.
SCENARIO 1 (the most common scenario): The culprit has not / only vaguely been seen, not reliably identified or not been perceived as a threat.
Indirect methods must be used to identify the cause, so that specific treatments can be selected and applied, and the need for supportive treatment can be predicted.
The pathway of Clinical Management
It is self-explanatory and based on common clinical sense.
Let us take a snakebite on the Indian subcontinent as an example.
If the snake has not been seen, the first step would naturally be to identify the prevalent species in the region where the accident occurred. The circumstances and behaviour of the bite may then provide further clues. If the patient exhibits signs and symptoms of envenoming, the pattern and progression of the clinical features (the effects of venom) should be examined, as these may provide further clues as to the identity of the snake responsible.
Set of biological tools
Distribution of venomous and poisonous Animals
at the place where the accident happened.
Biological features
The behaviour of the culprit and the circumstances under which the accident happened.
Set of clinical tools
Emergency Flowcharts
The emergency fowcharts illustrate patterns of clinical signs and symptoms, and guide immediate supportive emergency medical responses and help to identify the cause from the presenting clinical signs and symptoms.
Clinical Flowcharts
Clinical flowcharts illustrate how signs and symptoms evolve over time, ultimately leading to organ failure.
Clinical management
Clinical management provides key questions and guidance on the main diagnostic and therapeutic steps (both supportive and specific).
SCENARIO 2: The culprit has been reliably identified
Morphological identification
diagnosis, supportive and specific treatment
The 'Clinical Entries' sections provide diagnostic and therapeutic advice at the species level based on the latest evidence. This evidence base comprises studies, case reports, etc., and is stored and regularly updated.
Which diagnostic and therapeutic guidance is provided?
- The VAPA Guide provides the key clinical features and necessary emergency medical responses to envenoming and poisoning worldwide.
- It is not a textbook on emergency medicine. It assumes solid clinical knowledge and skills. Links to the SAMPLE and ABCDE approaches are provided, but other reliable sources of emergency medicine can also be used.
- Specific therapeutics: antivenoms and antidotes.
A multitude of antivenoms are produced to varying standards. The quality and accessibility of antivenoms that meet appropriate standards varies widely around the world.
Great efforts are being undertaken to secure appropriate standards (GMP) and access for people in need.
WHO: Snakebite envenoming - A strategy for prevention and control
WHO: Antivenoms
WHO Snakebite Information and Data Platform - The VAPAGuide does not provide a comprehensive list of the antivenoms available at a national or regional level, nor does it assess their quality or effectiveness. This would be impossible in such a fluid market.
The VAPAGuide refers to WHO-approved antivenoms (see above).
Antivenoms that are not manufactured to GMP standards or approved by the WHO are used at the attending physician's discretion and responsibility.
Classification of clinical envenoming and poisoning patterns.
We adopted a toxinological approach, relating observable clinical effects to the pathophysiology of envenoming and the primary targets of venoms and poisons in humans.
The following effects were considered:
- Autopharmacological effects
- Local effects
- Haematological effects
- Neurological effects
- Muscular effects
- Cardiac effects
- Renal effects
This categorisation attempts to distinguish between the primary and secondary effects of venoms and poisons. The primary effects of venom components can inform supportive therapeutic options and immediate life-saving interventions apart from antivenom therapy. And, also, when combined into envenoming patterns, venom effects help identifying a culprit that has not been (clearly) recognized.
This is straightforward in some cases and more challenging in others. For instance, the effects on the neuromuscular junction (i.e. interference with acetylcholine-based neurotransmission) are unambiguous. The subsequent clinical effects — muscular paralysis (including that of the respiratory muscles) leading to respiratory failure — are clearly primary.
In the case of other venom effects, distinguishing between primary and secondary effects is less clear-cut; the latter being the common final pathway when organ systems fail. Furthermore, the complex mixtures of active substances in venoms in many venomous and poisonous animals still need to be better understood.