Black mamba (Dendroaspis polylepis). Credit: John Marais
Mambas of the genus Dendroaspis pose a significant threat to public health across sub-Saharan Africa. Their bites trigger the rapid onset of severe and complex neurotoxic symptoms – such as involuntary muscle twitches, cardiovascular collapse and respiratory paralysis – which, without the timely administration of antivenom, can lead to death within just 45 minutes.
For the first time, researchers from Australia’s University of Queensland (UQ) have tested how the venoms of all 4 mamba species attack the nervous system and assessed the neutralising effects of 3 antivenoms commercially available in Africa.
Their findings reveal that mamba venoms are more complex than previously thought and finally explain why some bites tragically worsen after being treated with antivenom.
While treatment with existing antivenoms can address one kind of paralysis, they found that doing so unmasks a previously hidden paralysis which existing antivenoms consistently fail to counteract.
“The black mamba, western green mamba and Jameson’s mamba snakes aren’t just using one form of chemical weapon, they’re launching a coordinated attack at 2 different points in the nervous system,” explains senior author Bryan Fry from UQ’s School of the Environment.
“If you’re bitten by 3 out of 4 mamba species, you will experience flaccid or limp paralysis caused by postsynaptic neurotoxicity.”
The toxin binds to the nicotinic acetylcholine receptor to prevent the neurotransmitter acetylcholine from doing so. Acetylcholine plays an important role in muscle contraction and relaxation, so this results in weak or floppy muscles which are difficult to control.
“Current antivenoms can treat the flaccid paralysis but this study found the venoms of these 3 species are then able to attack another part of the nervous system causing spastic paralysis by presynaptic toxicity,” says Fry.
“We previously thought the fourth species of mamba, the Eastern Green Mamba, was the only one capable of causing spastic paralysis.”
They found that toxins within the venom enhanced the release of acetylcholine, which triggers constant muscle contractions and leads to spasms.
“This finding resolves a long-standing clinical mystery of why some patients bitten by mambas seem to initially improve with antivenom and regain muscle tone and movement only to start having painful, uncontrolled spasms,” says Fry.
“The venom first blocks nerve signals from reaching the muscles but after the antivenom is administered, it then overstimulates the muscles.
“It’s like treating one disease and suddenly revealing another.”
Further molecular analyses revealed that the spastic-paralytic and flaccid-paralytic toxins evolved in the mambas’ last common ancestor.
First author and UQ PhD candidate, Lee Jones, adds: “We also found the venom function of the mambas was different depending on their geographic location, particularly within populations of the Black Mamba from Kenya and South Africa.”
“This further complicates treatment strategies across regions because the antivenoms are not developed to counteract the intricacies of the different venoms.”
It’s estimated that as many as 500,000 snakebites occur each year in sub-Saharan Africa, resulting in about 30,000 deaths.
Black Mambas (Dendroaspis Polylepis) are of particular concern. As the only species of mamba typically lives on the ground and not in trees, with an extensive distribution across populated and agricultural areas, this increases the likelihood of fatal interactions with humans.
“This isn’t just an academic curiosity, it’s a direct call to clinicians and antivenom manufacturers,” Fry says.
“By identifying the limitations of current antivenoms and understanding the full range of venom activity, we can directly inform evidence-based snakebite care.
“This kind of translational venom research can help doctors make better decisions in real time and ultimately saves lives.”
The research has been published in the journal Toxins.