WHO publishes first-ever guidance on snakebite treatments
Geneva: Snakebite is responsible for some 83,000-138,000 deaths per annum. An additional 400,000 people per year suffer from disabilities such as amputations, scarring leading to impaired limb function and post-traumatic stress disorder.
The World Health Organization (WHO) estimates that 5.4 million people worldwide are bitten by snakes each year, with 2.7 million envenomings. In sub-Saharan Africa, the number of snakebite cases is estimated to reach 435,000-500,000 per year with 20,000– 32,000 deaths. Victims are from some of the least-empowered, poorest, and most-marginalized communities; often agricultural workers, rural villagers, and working children; in poorly constructed housing with very limited access to education and health care.
Snakebite envenoming can seem to be a complex disease to manage effectively. There are approximately 110 venomous snake species in Africa, but not all are medically important. Many of these species have very small geographical ranges and a low risk of human contact. Some of them have venom that is not considered dangerous to humans. Venoms are complex mixtures of multiple toxins and, depending on the type of toxins present in a venom, the physiological and pharmacological effects may vary considerably among and even within species. Fortunately, many of the toxins share broad immunological homogeneity such that neutralizing antibodies raised against one snake species are often effective against other species too.
To make the snakebite problems more manageable, some important intellectual and practical simplifications need to be considered.
WHO considers 24 species from 4 genera (Bitis, Dendroaspis, Echis and Naja) to be of the highest (Category 1) medical importance in sub-Saharan Africa and the major targets for antivenom products in the region. These are the venomous snakes that are most encountered and pose the greatest potential threat to human life and well-being. A further 24 species are of secondary (Category 2) medical importance, either because they are known to be highly venomous, but are either less frequently associated with serious snakebites or have little epidemiological data available.
Heterologous animal plasma-derived immunoglobulin preparations (“antivenoms”) have been the mainstay of treatment for snakebite envenoming for nearly 130 years and are the most effective drugs currently available for the treatment of snakebite envenoming. They are typically produced by immunizing donor animals such as horses or sheep with small amounts of snake venoms and then purifying antibody fractions from the hyperimmune plasma for intravenous administration to snakebite envenoming victims.
The quality, safety, and effectiveness of antivenoms are highly dependent upon the investment of producers in research and development, application of Good Manufacturing Practices (GMP) and rigorous quality control.
However, although antivenoms have been made for some 130 years and yet, remarkably, there has been until now, no guidance on how to design and manufacture a product of high quality that meets the correct requirements for safety, effectiveness, and functional use.
In order to improve the quality of antivenoms available in the market, WHO today published the first in a series of WHO public-benefit target product profiles (TPPs) for snakebite treatments. This is the first-ever guidance to improve the quality of such products. The TPP is a document that provides regulators, manufacturers, researchers and procurement agencies with essential information about the minimum and optimum characteristics of specific products for specific use cases, in this case, antivenoms used for the treatment of snakebites caused by various types of sub-Saharan African snakes. TPPs help to ensure that products are designed and manufactured to meet the match the clinical needs of populations at risk, and are “fit-for-use” – e.g., are safe, effective and adapted to the use environment.
A high-quality antivenom provides the best available treatment for approximately 5.4 million people who are bitten by snakes each year. Safe, effective antivenoms could prevent many of the 83 000-138 000 deaths caused by snakebites and reduce the severity of serious disabilities that impact many thousands more victims.
“Access to high quality, safe and effective antivenom is an issue of equity and this critical work brings us one step forward in being able to make this a reality” Dr Socé Fall, Director of the WHO Global NTD Programme.
Four TPPs for different types of conventional animal plasma-derived antivenoms
The first of these is for products that are intended for widespread use throughout sub-Saharan Africa, for treatment of snakebites irrespective of the species of snake causing the bite. The second is for the treatment of bites from a single species (or group) of snake(s). Products in both these categories are currently on the market.
The other two categories are for products that do not yet exist in sub-Saharan Africa, but evidence from other parts of the world suggests that if developed they may have a useful role to play. One of these new product types is for antivenoms where the snakebite mainly causes a syndrome dominated by neurotoxic effects, while the other is intended for non-neurotoxic snakebite syndromes that involve effects on blood clotting or tissue necrosis without paralytic effects.
These TPPs, are intended to provide guidance to manufacturers, regulators, procurement agencies, clinicians and researchers and will contribute to improvements in the quality, safety and effectiveness of antivenoms and thus better treatment of snakebites.
– global bihari bureau
