HUMP-NOSED PIT VIPER (Hypnale hypnale) is the second snake listed in WHO category 1 that doesn't belong to the "Big Four". The polyvalent antivenom available in India is not effective against this snake.
As "hypnales" are very common in Sri Lanka and the first cause of envenomation for the population, an antivenom for this snake is being developed in Sri Lanka (see abstract).
A few days ago I was looking at a video on endangered snakes in Goa area. The speaker referred to the hump-nosed pit viper bite as "an snake that you can be sick for 8 or 9 days and then fully recover, no problem". Well, maybe the speaker was trying to protect this snake from blind and irrational killing as it is happening nowadays too, just a guess. Anyhow, scientific papers describe fatalities also associated to HNPV envenomation.
There are several scientific clinical articles on patients that die after a Hump-nosed pit viper bite. Those fatalities, mainly due to kidney failure, have been recorded in Sri Lanka where this snake is very common, and also in Kerala, India.
As "hypnales" are very common in Sri Lanka and the first cause of envenomation for the population, an antivenom for this snake is being developed in Sri Lanka (see abstract).
A few days ago I was looking at a video on endangered snakes in Goa area. The speaker referred to the hump-nosed pit viper bite as "an snake that you can be sick for 8 or 9 days and then fully recover, no problem". Well, maybe the speaker was trying to protect this snake from blind and irrational killing as it is happening nowadays too, just a guess. Anyhow, scientific papers describe fatalities also associated to HNPV envenomation.
There are several scientific clinical articles on patients that die after a Hump-nosed pit viper bite. Those fatalities, mainly due to kidney failure, have been recorded in Sri Lanka where this snake is very common, and also in Kerala, India.
The title of the article says everything. I will summarize this study with what are to me the most relevant points. Please, refer always to the original article.
HUMP-NOSED PIT VIPER BITE: AN IMPORTANT BUT UNDER-RECOGNIZED CAUSE OF SYSTEMIC ENVENOMING
doi:10.1186/1678-9199-20-24
Shivanthan et al.: Hump-nosed viper bite: an important but under-recognized cause of systemic envenoming.
Journal of Venomous Animals and Toxins including Tropical Diseases 2014 20:24.
https://jvat.biomedcentral.com/articles/10.1186/1678-9199-20-24
Shivanthan et al.: Hump-nosed viper bite: an important but under-recognized cause of systemic envenoming.
Journal of Venomous Animals and Toxins including Tropical Diseases 2014 20:24.
https://jvat.biomedcentral.com/articles/10.1186/1678-9199-20-24
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| http://wildanimalsofindia.blogspot.in |
ABSTRACT: Hump-nosed viper bites are common in the Indian subcontinent. In the past, hump-nosed vipers (Hypnale species) were considered moderately venomous snakes whose bites result mainly in local envenoming. However, a variety of severe local effects, hemostatic dysfunction, microangiopathic hemolysis, kidney injury and death have been reported following envenoming by Hypnale species. We systematically reviewed the medical literature on the epidemiology, toxin profile, diagnosis, and clinical, laboratory and postmortem features of hump-nosed viper envenoming, and highlight the need for development of an effective anti-venom.
INTRODUCTION:
Hump-nosed viper (Hypnale) bite is an important yet under-recognized cause of morbidity and mortality in Southern India and Sri Lanka, where three species have been identified.
- India, Western Ghats:
- Hypnale hypnale
- Sri Lanka:
- Hypnale hypnale
- Hypnale zara (Sri Lanka only)
- Hypnale nepa (Sri Lanka only)
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| http://reptile-database.reptarium.cz/species?genus=Hypnale&species=hypnale&search_param=%28%28taxon%3D%27Crotalinae%27%29%29 |
It is the commonest cause of snakebite envenoming in Sri Lanka.
The authors performed a systematic review of the published literature.
EPIDEMIOLOGY:
Hypnale viper (HNV) accounts for 27 to 77% of venomous snakebites in Sri Lanka and south India. In Kerala, in 2007, were H. Hypnale was identified as a common and dangerous source of envenoming, second only to Russell's viper.
Sri Lanka: General findings from several hospital studies:
- Adults:
- Bites mostly men
- commonly at night, daytime
- Bites in feet or ankles, lower limbs
- near their homes, home garden (H. zara in the forest, H. nepa in tea estates).
- Children
- Feet and hand
- After provocation
- From 5 to 10 pm.
Low mortality was low (case fatality rate 1.7% in one study) always due to Acute Kidney Injury. In another study on 1543 patients, the systemic envenoming is described in 4.34% of patients, only two died. All fatalities are related to Hypnale Hypnale. Only one case of H. zara, none of H, nepa.
TOXIN PROFILE:
Potent cytotoxicity, weak neurotoxic and myotoxic activity, mild procoagulant activity and also phospholipase activity are present in HNV venom. There is an study (Maduwage K, 2011/2012) comparing the venom of the three subspecies of Hypnale which are common in Sri Lanka. The results suggest that the venom of Hypnale Hypnale is more toxic compared to the other two species.
DIAGNOSIS:
Identification of the snake by medical personnel viewing the dead snake or a photograph is the commonest means of diagnosing Hypnale snakebite. Misidentification commonly occurs between Russell's viper and the saw-scaled viper. Where the snake is unidentified, it is useful to diagnosed bases on key clinical features favoring HNPV like: local envenoming, incoagulable blood and renal failure; however, these are also provoked by Russell's viper.
(At present, there is no diagnostic kit for specific identification of Hypnale envenomation. Whole Blood clotting test is used to diagnose and monitor coagulopathy)
ENVENOMING:
Local effects (90% patients):
- Local pain, swelling, induration, local hemorrhagic blister formation, local bleeding, local necrosis, need for amputation and skin grafting, and regional lymphadenopathy have all been reported
Systemic envenoming:
- Coagulopathy:
- Oozing of blood from the site of the bite.
- Prolonged clotting time
- Low fibrinogen
- Increase of fibrinogen degradation products (FDP) / D-Dimer, in plasma
- Venom induced consumptive coagulopathy triad:
- Microangiopathic hemolytic anemia with
- thrombocytopenia and
- acute Kidney Injury.
- Renal toxocity, often requiring dialysis, and evolving to chronic renal failure requiring renal replacement therapy. Main cause of death after Hypnale snakebite.
- acute kidney injury, i.e., oliguria, dark urine, fluid retention, uremia and elevated serum creatinine.
- Thrombotic microangiopathy
- microangiopathic hemolytic anemia (MAHA),
- thrombocytopenia and
- severe anemia necessitating multiple blood transfusions,
- Neurological effects: not described.
- Heart: Transitory ECG changes, possibly related to electrolyte imbalance, and hemodynamic instability.
- Pulmonary effects: pulmonary edema has been documented.
- Gastrointestinal and liver effects: Nausea, vomiting, abdominal pain, hematemesis. Hepatic dysfunction non described.
TREATMENT:
Mainly symptomatic and supportive
General:
Antibiotics and Tetanus toxoid.
Local:
Analgesics, splinting of the bitten limb, wound care, and surgical management including skin grafting constitute the common approach employed against local envenoming. In rare cases, amputation may be needed.
Systemic envenomation:
Features of systemic envenoming are treated with supportive care.
Renal replacement therapy is the mainstay of management of acute renal impairment, and may become necessary if chronic kidney disease occurs consequently.
Optimized administration of blood components, correction of coagulopathy, and plasma exchange may be required when hematologic derangements occur.
No clear trial based evidence is available showing benefit of these interventions. There are no specific protocols for managing envenoming following HNV bite, and standard guidelines for snakebite management are followed.
ANTIVENOM:
No specific or polyvalent antivenom is available yet for human use in HNV envenoming [39]. The currently used polyvalent antivenom is ineffective in the treatment of HNV envenomation, and is associated with a high incidence of reactions.
The monovalent Calloselasma rhodostoma antivenom also is also capable of neutralizing the lethality and toxic activities of the venom, but its potency was lower .
CONCLUSIONS:
Formerly thought to result only in local envenoming, HNV bite can result in serious sequelae including death. Acute kidney injury and hematological manifestations are the predominant serious effects. Clinically significant neurotoxicity or cardiotoxicity does not occur. There are two key areas for future research: firstly, identification of clinical parameters and biochemical tests for early identification of systemic envenoming, i.e., early detection of coagulopathy and nephrotoxicity; secondly, the development of an efficacious specific antivenom for routine use.
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Hypnale Hypnale in Kerala. Have the abstract only.
FIRST AUTHENTICATED CASES OF LIFE-THREATENING ENVENOMING BY HUMP-NOSED PIT VIPER (Hypnale hypnale) IN INDIA.
J.K. Joseph, ID Simpson, CNS Menon, Jose KJ Kulkarni, GB Raghavendra, DA Warrell
Trans R Soc Trop Med Hyg (2007), 101 (1): 85-90
Summary
In Kerala, south-western India, five patients developed systemic envenoming after bites by hump-nosed pit vipers (Hypnale hypnale), proved by identification of the snakes responsible. Two of the dead snakes had been misidentified as saw-scaled vipers (Echis carinatus), while three had remained unidentified. Symptoms of local envenoming were pain, swelling, haemorrhagic blistering, bruising and regional lymphadenopathy. Systemic symptoms included headache, nausea, vomiting and abdominal and chest pain. There was evidence of haemostatic dysfunction (coagulopathy, fibrinolysis, thrombocytopenia or spontaneous systemic haemorrhage) in all cases and of microangiopathic haemolysis in two. Two patients were haemodialysed for acute renal failure, one of whom developed pulmonary oedema requiring mechanical ventilation. In India, H. hypnale has not previously been regarded as a cause of frequent or potentially dangerous envenoming. Its medical importance has been overlooked throughout its geographical range, probably because of confusion with other small species. No specific antivenom exists, yet most patients are treated with non-specific antivenoms, risking reactions without hope of benefit. An effective antivenom is urgently needed in south India and in Sri Lanka, where this species is also a common cause of bites.
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Here a wonderful new: a polyspecific antivenom is developed for Sri Lanka and will include Hypnale! I love this kind of news!!!
Toxicon 117:103 · July 2016.
This is an Open Access journal.
A POLYSPECIFIC ANTIVENOM FOR SRI LANKA: FIRST TO INCLUDE HYPNALE
D E. Keyler 1,2, I. Gawarammana 3, M. Villalta 4, G.
Leon 4, K. H. Sellahewa 5, K. McWhorter 1, R. Malleappah 1, S. A. Weinstein 6, J. M. Gutierrez 4. 1 Animal Venom Research International (AVRI), CA, USA; 2 Department of Experimental and Clinical Pharmacology, University of Minnesota, USA; 3 Department of Medicine and South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Sri Lanka; 4Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San Jose, Costa Rica; 5South Asian Institute of Technology and Medicine, Sri Lanka; 6Women’s and Children’s Hospital, Adelaide, Australia
E-mail address: keyle001@umn.edu
Introduction:
Snakebite envenoming is a significant medical problem in
Sri Lanka, with an estimated 40,000 hospital admissions annually. Despite
the magnitude of this problem, there is no antivenom that has been
developed derived from the venom of Sri Lankan snakes. Moreover, there
is no antivenom specific for Hypnale spp. (H. hypnale, H. nepa, H. zara),
viperid species reported to account for 22-77% of snakebite patients in the
country. Hypnale species, commonly called Merrem’s hump-nosed pit viper, or kunakatuwa (Sinhala), are ubiquitous in distribution, being prevalent in tea, rubber, coconut plantations, and home gardens. Envenomation
is rarely fatal, but significant morbidity is frequent. Hematological, nephrotoxic, and cerebral infarction have been reported. Venom analyses reported for all three Hypnale species have shown varying degrees of
procoagulant activity, potent cytotoxic effects, and myotoxic, neurotoxic,
and phospholipase A2 activities. Recent in vivo research in Sri Lanka has
provided preliminary data suggesting potential Hypnale species-specific
venom differences that influence the severity of clinical manifestations in
envenomated patients. Para-specific protection against Hypnale venom-induced coagulopathic effects and lethality in animals by Malayan pit viper
(Calloselasma rhodostoma) antivenom suggests the presence of similar
venom antigens in the different genera; however, clinical efficacy in
envenomated patients is unproven.
Methods:
A partnership to develop a Sri Lanka antivenom has involved
academic groups (University of Peradeniya and Instituto Clodomiro Picado,
University of Costa Rica), a non-profit public charity from the USA (Animal
Venom Research International-AVRI), and a public antivenom manufacturer (Instituto Clodomiro Picado (ICP), University of Costa Rica).
A basic
toxicological characterization of Sri Lanka snake venoms has been performed using conventional laboratory assays at ICP. In parallel, horses have
been immunized with the venoms of Daboia russelli, Echis carinatus,
Hypnale hypnale and Naja naja, and a pilot batch of antivenom has been
produced, which has been evaluated for its preclinical efficacy against
these venoms.
Results: This antivenom compares favorably with the currently used Indian antivenom; however, there is no comparison that can be made for
Hypnale. A research clinical trial is to be conducted in 2016 in Sri Lanka
which will involve a non-placebo treatment arm for Hypnale to evaluate
antivenom safety and efficacy.
Key Words: Antivenom, Hypnale, Sri Lanka
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This is the continuation of the study. I will summarize the article with main reference to the Hypnale data. Please always refer to the original.
Toxicon Vol 122, November 2016, pages 152-159
DEVELOPMENT OF A NEW POLYSPECIFIC ANTIVENOM FOR SNAKEBITE ENVENOMING IN SRI LANKA: ANALYSIS OF ITS PRECLINICAL EFFICACY AS COMPARED TO A CURRENTLY AVAILABLE ANTIVENOM.
Mauren Villalta a, Andres Sanchez a, María Herrera a, Mariangela Vargas a, Alvaro Segura a,
Maykel Cerdas a, Ricardo Estrada a, Indika Gawarammana b, Dan E. Keyler c, d,Kimberly McWhorter c, Roy Malleappah c, Alberto Alape-Giron a, Guillermo Leon a,Jose María Gutie rrez a, *
a Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San Jose, Costa Rica
b Faculty of Medicine, University of Peradeniya, Sri Lanka
c Animal Venom Research International, Moreno Valley, CA, USA
d Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA
a Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San Jose, Costa Rica
b Faculty of Medicine, University of Peradeniya, Sri Lanka
c Animal Venom Research International, Moreno Valley, CA, USA
d Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA
ABSTRACT:
A new whole IgG, freeze-dried, polyspecific antivenom was prepared from the plasma of horses immunized with the venoms of the snakes
A new whole IgG, freeze-dried, polyspecific antivenom was prepared from the plasma of horses immunized with the venoms of the snakes
- Daboia russelii,
- Echis carinatus,
- Hypnale hypnale, and
- Naja naja from Sri Lanka.
The activities tested were: lethality, hemorrhagic, in vitro
coagulant, proteinase and phospholipase A2. Both antivenoms neutralized, to a different extent, these
activities of the venom of D. russelii, E. carinatus, and N. naja. In general, the polyspecific Sri Lankan
antivenom was more effective than the Indian antivenom in the neutralization of the venoms of D.
russelii and E. carinatus, whereas the Indian antivenom showed a higher efficacy against the venom of N.
naja.
Regarding H. hypnale, the new Sri Lankan antivenom was effective in the neutralization of all activities tested, whereas the Indian antivenom neutralized lethality but not hemorrhagic, coagulant,
proteinase and PLA2 activities, in agreement with the fact that this venom is not included in the immunization mixture for this antivenom.
Results suggest that the new polyspecific Sri Lankan antivenom
has a satisfactory preclinical neutralizing profile and compares favorably with the Indian antivenom. This
is ready to be tested in a clinical trial to evaluate its efficacy and safety in human victims of snakebite
envenomings by D. russelii, E. carinatus and H. hypnale in Sri Lanka.
AS THIS IS A QUITE LONG STUDY, I'M JUST SHOWING THE ABSTRACT AND WOULD GO THROUGH IT ON THE NEXT POST.
ॐ लोकाः समस्ताः सुखिनो भवन्तु ॥
Om Lokah Samasthah Sukhino Bhavantu
May all beings everywhere be happy and peaceful.
