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Photo credit; DA Warrell |
Starting with a simple DNA swab
taken from fang marks on people bitten by snakes, an international research
team correctly identified the species of the biting snake 100 percent of the
time in a first-of-its-kind clinical study, according to data presented today
at the American Society of Tropical Medicine and Hygiene's (ASTMH) Annual
Meeting.
The study, conducted at three
medical facilities in Nepal, found that if snake DNA could be isolated from the
bite wound, the test identified the species of snake responsible every time.
"These findings represent a
significant step toward improving care for patients in areas of the world where
snakebites constitute a massive but neglected health risk," said François
Chappuis, MD, PhD, chief of the division of tropical and humanitarian medicine
at Geneva University Hospitals, Switzerland, who directed the study and
presented the results. "This DNA test may hasten more effective bedside
diagnostics for snakebite victims, giving them a better chance of surviving and
making a full recovery."
Bites from venomous snakes are
common in many parts of the world and an especially serious unresolved health
problem to millions of people living in South and Southeast Asia, as well as
Africa and Latin America. Although there are no reliable numbers at the global
scale, a study published in 2008 estimated at least 421,000 cases of
envenomation and up to 94,000 deaths occur worldwide from snakebite each year.
However, experts warn that these figures may underestimate the real problem,
which is believed to affect several million people bitten by venomous snakes
annually and hundreds of thousands who die or survive disabled, suffering from
amputation or deformed limbs as a result of unavailable or delayed treatment.
In some villages of the study area
of southeast Nepal reported today, a community-based survey in 2002 revealed an
estimated 1,162 snakebites and 162 snakebite deaths per 100,000 people per
year, one of the highest rates ever reported. Likewise, a recent survey of more
than one million deaths in India, published in the journal PLoS Neglected
Tropical Diseases in 2011, found that 46,000 people die every year in India
from snakebites. This figure is about 20 times the official death toll recorded
in Indian hospitals, most likely because less than one in four fatal snakebite
cases had received any hospital treatment, the study revealed.
"People bitten by snakes in
South Asia often do not seek treatment at a medical facility, and if they do,
the vast majority don't take the snake to clinics, although it is often killed,
and can't identify the species that bit them," Chappuis said. "Yet
knowing the species of snake is critical to determining the best course of
treatment."
In Nepal, for example, cobras and
kraits are among the most common venomous snakes. Their venoms attack the
nervous system and can be fatal. Patients bitten by either snake have similar
symptoms, such as nausea, headache, drowsiness and limb as well as respiratory
paralysis. However, the toxins of these snakes and their mechanisms of action
differ, and so does the response to antivenom and other drugs. For example, the
locally available antivenom has limited or no efficacy against krait
envenomation, which often leads to useless repeated doses resulting in
increased cost and--possibly--adverse side effects, explained Chappuis. Also,
bites by cobras and kraits lead to different complications that the attending
physicians need to prevent or be prepared for. Therefore, positive
identification of the biting species becomes important to effective treatment.
Preliminary results presented today
show that among 194 bite-site DNA samples collected in Nepal during the study,
87 were from a venomous species. The spectacled cobra accounted for 42 bites
and the common krait for 22. In 21 cases, the patients brought the dead snake
with them, and in those cases expert examination of the snake and the DNA test,
performed by different investigators, independently provided the correct
identification. Snake DNA could be obtained from about one in four bite wounds.
According to the researchers, one factor that excluded samples was if the
patient attempted folk or home remedies tampering with the bite site prior to
arriving at the medical clinic.
The research team also correlated
clinical symptoms with the species biting patients. They found that krait bites
happened more often at night, indoors, or while people were sleeping, while
cobra or pitviper bites were more likely to cause swelling at the bite site.
The technique also identified several species of non-venomous snake involved in
bites.
"The proportion of
non-venomous snakes that bite people is actually rather high," said Ulrich
Kuch, PhD, of the department of tropical medicine and public health in the
Institute of Occupational, Social and Environmental Medicine of Goethe
University (Frankfurt, Germany), and developer of the snake DNA identification
test. "Snakebite patients are kept in the hospital for 24-hour
observation, which strains healthcare resources in many countries. By
identifying species of nonvenomous snake, it is also possible to assist the
local people and avoid hospital stays for those not at risk of
envenomation."
The research team is currently
developing a rapid diagnostic "dip-stick" test similar to a pregnancy
test that could be used to rule out certain common venomous snakes and help
physicians more quickly decide the best course of treatment. Conversely, if for
example, krait venom is detected, doctors could quickly give antivenom instead
of waiting for clinical signs of envenomation, as is current practice. They
would also accelerate the transfer of patients to referral hospitals with
intensive care units able to ensure adequate respiratory support. Such a test
would be easy to administer in rural healthcare settings with limited
resources, said Chappuis.
"That's where the recently
developed DNA test could be most valuable," he added. While the DNA test
is labor intensive and time consuming, making it impractical for day-to-day
clinical use, its high accuracy could allow it to become a "gold
standard" in clinical studies of rapid diagnostic tests under development.
In addition, the DNA test could become a powerful epidemiological tool to
determine which species of snake bite people in various tropical regions.
"Knowing the distribution of
snakes and the number of snakebites within a region could help improve
allocation of scarce antivenoms to areas where they are most needed" said
Chappuis.
The researchers have completed
small clinical studies in Nepal and Bangladesh and are preparing a larger
multi-center clinical study using the DNA test in Myanmar and Nepal, countries
with among the highest rates of snakebite deaths. The current study is funded
by the UBS Optimus Foundation and the Swiss National Fund.
"We need new tools in order to
save more lives," said Sanjib K. Sharma, MD, professor of medicine at the
B.P. Koirala Institute of Health Sciences in Nepal, and the principal
investigator of the study. "There is gross disparity in the management and
outcome of snakebites since most occur in rural, agricultural areas while the
great majority of healthcare workers are in urban locations."
"Most people are unaware that
snakebite is a very real and serious threat both to the health and economic
vitality of rural communities throughout much of the developing world,"
said Alan J. Magill, MD, FASTMH, president of the American Society of Tropical
Medicine and Hygiene. "This innovative research may be enabling for the
development of a point of care test to positively identify biting snakes.
Accurate diagnosis would go a long way toward documenting the impact of
snakebite and improving medical care for this often neglected yet pervasive
problem."
Citation
Sharma SK, Kuch U, Höde P, Bruhse L.
Pandey D, Chappuis F, Alirol E. 2014. Use of clinical predictors and molecular
diagnosis to identify the species responsible for snakebite in rural Nepal. AmericanSociety of Tropical Medicine and Hygiene (Burness Communications).
Abstract. ASTMH 63rd Annual Meeting Nov. 2-6. New Orleans.