The Antivenom Crisis

The availability and appropriate use of effective antivenom is the most important tool in management of snakebite envenoming and without this essential drug mortality will remain high. Despite the high prevalence of snakebites and a high demand of antivenom for treatment, the availability of effective antivenom is declining. A decline in production, a loss of confidence in the products, and the underutilisation of proven life-saving antivenom products have marked the past decades.

The problems of snake antivenom

As poor and marginalized populations are particularly affected by snakebites, the market incentive to research and produce antivenoms is low. Antivenoms are often specific to one or a few snake species, whose distribution is restricted to smaller geographical regions. These antivenoms are only useful for a restricted population living in the specific area, thus making research and production less appealing from a commercial point of view.

Antivenoms are usually equine or ovine-derived serum products, and the production is complex and expensive. Preclinical and clinical testing, registration in individual countries are further hurdles that prevent companies to initiate development and production.

As a result of the lack of effective antivenoms, multiple antivenoms have been registered that lack transparent clinical, or even preclinical testing. Using ineffective antivenoms leads to a further loss of confidence in antivenom treatment. Therefore, more uniform regulation and execution of preclinical and clinical studies and licensing would be beneficial. For the African continent, the newly introduced African Medicines Agency (AMA) in Rwanda could be a way to improve the situation. Further, only a small proportion of antivenom is manufactured for international use, while most manufacturers produce only for national or regional use. This points to the importance of local production, which should be encouraged, especially in countries where snakebites are prevalent. As seen on the map on the right, this is especially needed for the African continent where the incidence of snakebites is high but local production is very low.

Alternative text: The image shows a white world map with country outlines. Some countries are coloured in red, these countries have no local antivenom production. Most of these countries are on the African continent, but also in Europe, Middle-East, Asia and Central America.
Countries with no local antivenom production, https://www.who.int/teams/control-of-neglected-tropical-diseases/snakebite-envenoming/antivenoms
© WHO 2017

The “vicious cycle”

Why this crisis persists and how it leads to the aforementioned loss of confidence and underutilisation of antivenom products can be explained by the “vicious cycle”. The initial situation is a low supply of antivenom, and subsequently, high prices for antivenom. This often leads to cheaper - and often less effective or even counterfeit - antivenom being used to treat patients with snakebite envenoming. This causes a loss of confidence in antivenom products, leading to underutilisation of antivenom. When a snakebite happens, patients are more likely to seek traditional healers, and demand for antivenom continues to decline. This results in a further market loss for antivenom suppliers, driving prices even higher while supply decreases further.

 

The possible solutions

Clearly, there is no single solution to the antivenom crisis, but a mix of measures that support each other is needed. Two such measures are an increased local production of Antivenom and increased coordinated approval of Antivenom. Antivenom on the market must have demonstrated efficacy in preclinical and clinical trials. This also requires strengthening research capabilities.

Sufficient production of antivenom must go hand in hand with the expansion of Universal Health Coverage (UHC), which would ideally cover the cost of treatment. This will improve access to antivenom, keeps the demand high and is the key to reduce mortality. In addition, logistical innovations, such as distribution of antivenom through drones from a central storage, can be a lever to reach and treat people everywhere.

The picture shows a pie chart that is divided into 5 different sections. At each section is an arrow pointing right in the circle to the next section. The first section says "High prices for and low supply of antivenom". The second section says “Cheaper antivenom is often less effective or not effective at all”. The next section says “Traditional healers are consulted”. The fourth section says “Demand for antivenom decreases” and the final section before arriving at the beginning again, says “Market loss of and loss of confidence in antivenom”.
The vicious cycle of antivenom market decline, adapted from Médecins Sans Frontières https://www.msf.org/snakebite
© RG Snakebite Envenoming