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Black mamba dendroaspis polylepis bite: a case report

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Although very rare in a European context, a bite from the black mamba Dendroaspis polylepis is an event that poses an immediate threat to life. Given the content of neurotoxins in the snake's venom, the mortality of envenomation reaches 100% in almost every case if ventilation is not provided in a timely manner and adequate therapy initiated. The report describes a case of a snake breeder being envenomed. This 31-year-old man was bitten by a black mamba on his finger, and who subsequently developed clinical symptoms of envenoming typical for the species. Thanks to mechanical ventilation being employed promptly, with myorelaxation during generalized muscle fasciculations, and particularly owing to the eventual antivenin therapy, the patient's condition settled without consequences. In addition to describing the given case in detail, the paper discusses the composition and mechanisms of action of black mamba venom, while providing guidelines for adequate therapy.
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Závada J.; Valenta J.; Kopecký O.; Stach Z.; Leden P.
298) Prague Medical Report / Vol. 112 (2011) No. 4, p. 298–304
© Charles University in Prague – Karolinum Press, Prague 2011
Black Mamba Dendroaspis Polylepis Bite:
A Case Report
Závada J., Valenta J., Kopecký O., Stach Z., Leden P.
Department of Anesthesiology and Intensive Care, First Faculty of Medicine,
Charles University in Prague and General University Hospital in Prague, Prague,
Czech Republic
Received June 22, 2011; Accepted September 26, 2011.
Key words: Black mamba Dendroaspis polylepis – Snake bite – Muscle paralysis –
Mechanical ventilation – Mamba antivenin
Abstract: Although very rare in a European context, a bite from the black mamba
Dendroaspis polylepis is an event that poses an immediate threat to life. Given
the content of neurotoxins in the snake’s venom, the mortality of envenomation
reaches 100% in almost every case if ventilation is not provided in a timely
manner and adequate therapy initiated. The report describes a case of a snake
breeder being envenomed. This 31-year-old man was bitten by a black mamba
on his nger, and who subsequently developed clinical symptoms of envenoming
typical for the species. Thanks to mechanical ventilation being employed promptly,
with myorelaxation during generalized muscle fasciculations, and particularly
owing to the eventual antivenin therapy, the patient’s condition settled without
consequences. In addition to describing the given case in detail, the paper discusses
the composition and mechanisms of action of black mamba venom, while providing
guidelines for adequate therapy.
Mailing Address: Jiří Valenta, MD., Department of Anesthesiology and Intensive
Care, First Faculty of Medicine, Charles University in Prague and General
University Hospital in Prague, U Nemocnice 2, 128 08 Prague 2, Czech Republic;
Phone: +420 224 962 248; e-mail: jiri.valenta@vfn.cz
Black Mamba Bite
Prague Medical Report / Vol. 112 (2011) No. 4, p. 298–304 299)
Introduction
With an average length of 250–350 cm, and the maximum recorded length of
425 cm, the black mamba Dendroaspis polylepis is the longest venomous snake
in Africa. In reality, this snake possesses an olive-brownish through to dark gray
colour and a light belly; the name is actually derived from the black colour inside
its mouth. Mambas are considered one of the fastest snakes either when moving
or possibly striking when disturbed, which makes them highly dangerous creatures
when combined with their short-tempered behaviour (Figure 1). The genus
members compete with the African puff adder Bitis arietans and saw-scaled vipers
Echis sp. for the dubious honour of supremacy in terms of mortality from bites
in Africa, based on lethality reaching 100% if no therapy is available. However, the
incidence of snake bites in typical places of envenoming is probably overstated
(Warrell, 1995; Hodgson and Davidson, 1996; Valenta, 2010).
The black mamba’s venom glands contain approximately 8–16 ml of liquid venom.
In the freshly hatched young, the amount is 1–2 ml of venom, which is sufcient
quantity for a lethal effect on a human. The key venom components involve
highly effective neurotoxins. In this species, the venom contains neurotoxically
acting nicotine acetylcholine receptor antagonists analogous to the postsynaptic
neurotoxins of other elapids (Elapidae) classied as α, β, γ and δ neurotoxins
(Hodgson and Davidson, 1996). The neurotoxins with the greatest effectiveness are
dendrotoxins (DTX); blocking voltage potassium channels, these cause extension
of the process of re-polarization of neurons (Harvey and Karlsson, 1980; Harvey,
2001; Harvey and Robertson, 2004). This way the substances support muscle
paralysis by exhausting neuromuscular junctions via super-threshold stimulation.
Other types of neurons include fasciculins, peptide acetylcholinesterase inhibitors.
Originally isolated from the venom of the green mamba (Tox-C isolated from the
venom of the black mamba), these substances increase the intrasynaptic quantity of
Figure 1 – Black mamba
Dendroaspis polylepis
(photo: P. Velenský).
Závada J.; Valenta J.; Kopecký O.; Stach Z.; Leden P.
300) Prague Medical Report / Vol. 112 (2011) No. 4, p. 298–304
acetylcholine, which results in muscle fasciculations (Karlsson et al., 1984; Warrell,
1995; Hrdina et al., 2004). Some of the peptides isolated from mamba venom
act as muscarine acetylcholine receptor ligands and probably potentiate neural
transmission in CNS (Jolkkonen et al., 1995).
The venom also contains a certain portion of components that are cardiotoxic
(Naidoo et al., 1987). Hyaluronidases facilitate rapid propagation of venom
components in the organism, plus there is the Dendroaspis natriuretic peptide
(DNP), a substance analogous to the atrial natriuretic peptide in humans; it is
responsible for causing diuresis through natriuresis and dilation of vessels (Lee
and Burnett, 2007). Hemolytic, hemorrhagic and coagulation activities are almost
completely absent from mamba venom (Warrell, 1995).
Case report
A 31-year-old Czech snake-breeding specialist and active sportsman experienced a
snake bite from a black mamba on the tip of the third nger of his right hand; the
bite occurred through the cloth of a snake transporting bag. First aid procedures
were carried out by the patient, which involved cutting next to the bitten site
and applying Sutherland’s pressure immobilization bandage (whole extremity tight
bandage). Being aware of the severity of his status, the man arranged for immediate
transportation to the local hospital.
Fully conscious in the emergency room, the patient was showing tachycardia
of 150–160 per minute, hypertension (systolic blood pressure of 200 mm Hg)
and profusive sweating, with paresthesia in the lower limbs and dyspnea. Due to
increasing respiratory failure, the patient was intubated and mechanical ventilation
initiated with continual analgosedation; the man was admitted to ICU. Following the
intubation, furosemide and manitol were administered due to signs of pulmonary
edema, with a subsequent application of hydrocortisone and antitetanic prophylaxis.
After consulting the Toxinology Center, the patient was transferred par avion to
their ICU under continued sedation, ventilation, and intermittent muscle relaxation.
Upon admission to the ICU, which took place 4.5 hours after the bite, limb
and body muscle fasciculations appeared upon reducing such relaxation, despite
intense sedation using propofol and sufentanil. The patient was continually profusely
perspiring and hemodynamically unstable, with a sinus tachycardia of 125 per
minute, centralized circulation and decreased capillary rell. A slight decrease
in blood pressure was treated by volumosubstitution and also temporarily by
administering a low dose of norepinephrine (less than 0.1 μg/kg/min); at the same
time, peripheral perfusion was improving. No pathological ndings were found via
echocardiography. Mechanical ventilation with a PEEP level of 6 cm H2O and FiO2
of 0.4 was sufcient to maintain normal levels of blood gases. Polyuria with diuresis
was developing, as much as 500 ml per hour. The limb was without any hematoma
and oedema and was kept bandaged until administering the antivenom – SAIMR
polyvalent antivenin, South Africa – of which two doses were applied.
Black Mamba Bite
Prague Medical Report / Vol. 112 (2011) No. 4, p. 298–304 301)
Despite the fact that two doses of antivenin had been applied, fasciculations
became generalized nine hours following the bite, with increased CO2 production
and body temperature. The status did not change even when sedation was
intensied using diazepam, midazolam, thiopental and after giving MgSO4.
Fasciculations receded only following relaxation by means of administering
atracurium in the form of a bolus, and this at full dosage (0.5 mg/kg). Redness
on the skin became apparent, which in this phase was not accompanied by
perspiration, plus there were rather striking reddish bands around peripheral veins
on the affected limb and a slight swelling developed on the injured nger. Even a
third dose of antivenin did not result in mitigating the symptoms. Fears of potential
development of rhabdomyolysis and myoglobinuria, with creatinkinase levels
registering 10.81–20.80 μkat/l, meant relaxation of the patient had to be
conducted on a continual basis. The levels of serum myoglobin did not exceed
407 mg/l.
Additional antivenin had to be brought in urgently from a foreign toxicological
centre. 27 hours after the bite two more doses of antivenin were administered,
the continual relaxation by atracurium halted and the dosage of analgosedation
decreased. Later, the fasciculations stopped, 3 hours after administering the
last dose of antivenin. 35 hours following the bite, respiratory muscle function
recovered, the extent of which was, however, insufcient for the extubation.
Mechanical ventilation was shifted to ventilatory support.
In laboratory testing, leukocytes were found to have increased during the
envenomation, with 15.07×109/l being the maximum, plus progressive growth in
CRP occurred, the levels ranging from 1.3 mg/l to 241.6 mg/l.
On day 4, i.e. the 58th hour following the bite, the patient was extubated, with
muscular strength proving sufcient. The diffuse redness receded, with the limb’s
swelling temporarily progressing to the mid forearm. The patient was observed
over the next 24 hours until full extent of mobilization was reached with the
remission of neurological symptomatology and once hemodynamic stability was
achieved and per os intake recovered. The oedema regressed with only localized
extension on the nger. On day 5, the patient was transferred to the neurological
department of his local hospital, after two days of observation dismissed home fully
recovered.
Discussion
A bite by the mamba is a rare event within Europe and only involves snake
enthusiasts. In fact, just one case of envenomation by a black mamba has
been described and published in the past 30 years throughout the continent
(Markwalder and Koller, 1987). Two case studies describe bites by a different
member of the genus, the green mamba Dendroaspis viridis (Markwalder and
Koller, 1987; Leclerc et al., 2008). In these, however, the effect of neurotoxins
was not serious enough to result in paralysis of the respiratory muscles and
Závada J.; Valenta J.; Kopecký O.; Stach Z.; Leden P.
302) Prague Medical Report / Vol. 112 (2011) No. 4, p. 298–304
mechanical ventilation was not required. No antivenin was administered due to
the mild progress experienced and prior recurrent exposure to a horse antivenin
(Markwalder and Koller, 1987), whilst in the case described by Leclerc et al. (2008)
progress also proved mild and no antivenin was available. Other than these, a few
cases of envenoming by mamba bites have been published in Africa (Crisp, 1985;
Harvey, 1985; Hilligan, 1987).
The high efciency of toxins contained in black mamba’s venom causes life-
threatening muscular paralysis to develop even when the quantity of venom
injected is low, and this within several minutes following the bite. If symptoms
develop, arrangements for mechanical ventilation and subsequent nal treatment
by administering the respective antivenin are, in a European context, requirements
for successful therapy. When there is a lack of options to ensure ventilation for the
affected person, very timely application of a sufcient dose of antivenin is essential,
which may prevent the effects of neurotoxins from fully developing, as well as
avoiding paralysis of the respiratory muscles and ventilatory failure (Warrell, 1995).
Even though the injury occurred through a transporting bag and just a single
fang was employed, and assuming that only a minor quantity of venom had been
transferred, the severity of the envenomation is conrmed through the possible
lethal effect of just a fraction of the quantity of venom that an adult black mamba
can release. Symptoms of afiction were developing as early as during the patient’s
transfer. The autonomic and circulatory symptoms that occurred can be attributed
to the effects of venom components, but also in part to the current mental state of
the person affected. Nausea, vomiting, abdominal pain, headache, perspiration, and
vasomotoric disorders are conditions generally described in cases of envenoming
by a snake bite, which applies to one from the mamba as well (Warrell, 1995).
The onset of neurological symptoms usually begins with paresthesia and paralysis
in the area of the cranial nerves, with subsequent progression craniocaudally. The
elimination of respiratory muscles and respiratory insufciency usually occurs while
maintaining full consciousness. In the case described, the development of this life-
threatening symptomatology took place within 30 minutes.
The progression of neurotoxic effects with apparent and persisting fasciculations,
despite administering the rst allocation of the available antivenin, heightened
concerns about damage to the neuromuscular plate and axons in the instance of
long-term, excessive stimulation by dendrotoxin (DTX) and fasciculins. Due to the
reasons above, additional doses of antivenin were ordered urgently from abroad.
Potential damage to muscle cells by fasciculations was another concern. Continual
myorelaxation to eliminate ongoing muscle fasciculations proved to be temporarily
sufcient therapy to protect the muscular tissue and bought some time before the
other doses of antivenin were supplied.
Administering cholinesterase inhibitors, like edrofonium or neostigmine (Warrell,
1995; Hodgson and Davidson, 1996), effective in cases of postsynaptic neurotoxin
effects and as recommended by some authors, was not applied because it was not
Black Mamba Bite
Prague Medical Report / Vol. 112 (2011) No. 4, p. 298–304 303)
indicated under the action of neurotoxins that increase acetylcholine supply on
neuromuscular junctions, i.e. DTX, fasciculins, with the potential consequence of
intensifying the effects of these.
The high diuresis in the initial phase of envenomation can be associated with
the presence of DNP, a polypeptide with natriuretic effects, and even with
administration of furosemide and manitol during treatment at the local hospital due
to suspected development of pulmonary oedema and prevention of tissue oedema.
The cause of the occurrence of the pulmonary oedema is not explained by the
presence of any of the described components of the black mamba’s venom; it,
however, might be associated with severe autonomic responses and hemodynamic
instability, or the possible content of some enzymatic components of the
metalloprotease type that may generally interfere with the endothelial structure
and that of its junctions.
Conclusion
The case described above illustrates a typical severe progress in envenoming by
the black mamba. The total quantity of antivenin used for neutralizing the venom
components indicates, as well as the mechanism of the bite, that the quantity of
venom released was rather small. Despite the facts above, severe envenomation
posing an immediate threat to life developed, which is consistent with the toxicity
considered and described in the black mamba venom. A key moment in the case
of snake bite from the black mamba is timely reaching a medical facility that can
arrange for securing the airways and mechanical ventilation, plus the adequate
antivenin must be available.
References
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... Green-gray variants occur in juvenile black mamba's [6,9]. The length of an adult specimen varies from approximately 2 to 4 meters and it can move up to 20 km/h [3,6,[8][9][10]. D. polylepis primarily lives in forested savanna or in riverine forest, predominantly in areas with rocky hills. ...
... Of eight case reports describing an electrocardiogram (ECG) [9,10,[21][22][23]26,28,40] seven had at least one ECGabnormality [6,10,21,23,26,28,40]. Tachycardia seen on an ECG is also considered an ECG-abnormality. ...
... Of eight case reports describing an electrocardiogram (ECG) [9,10,[21][22][23]26,28,40] seven had at least one ECGabnormality [6,10,21,23,26,28,40]. Tachycardia seen on an ECG is also considered an ECG-abnormality. ...
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Context The black mamba (Dendroaspis polylepis) is, due to its extremely toxic venom, one of the most dangerous snake species in Sub-Saharan Africa. A D. polylepis bite is a medical emergency and requires adequate action to prevent severe complications. However, there are no comprehensive reviews available based on clinical cases, and no readily accessible guidelines for standardized treatment. Therefore, we aim to provide an overview regarding the currently available clinical literature on D. polylepis envenomations; in order to promote knowledge on symptomatology and treatment options. Methods We searched for cases reporting humans bitten by D. polylepis in PubMed, Embase, Scopus, and Sabinet. We searched the reference lists of all eligible articles for additional articles. After quality assessment, 29 cases were included in this review. We used descriptive analysis to create an overview of the collected parameters. Discussion Among the included case reports and case series, D. polylepis envenomations most frequently resulted in decreased respiratory function, sweating and paralysis. The onset of symptoms usually occurred within 60 minutes. Neurological symptoms occurred more often than symptoms of autonomic dysfunction. In the reported cases most patients (26/29) received antivenom and most survived (25/29). We recommend the reporting of additional structured case reports to improve future analyses on the clinical course of envenomations, in order to improve public health response to D. polylepis envenomations.
... administrando-se norepinefrina (Erulu et al., 2018;Valenta, 2011). Em caso de edema agudo do pulmão a administração de manitol e furosemida e a subsequente administração de hidrocortisona e vacina antitetânica têm-se mostrado muito benéficos devendo a entubação e ventilação ser feita com sedoanalgesia, de preferência numa unidade de cuidados intensivos tal como ocorreu no caso clínico apresentado (Erulu et al., 2018;Valenta, 2011). ...
... administrando-se norepinefrina (Erulu et al., 2018;Valenta, 2011). Em caso de edema agudo do pulmão a administração de manitol e furosemida e a subsequente administração de hidrocortisona e vacina antitetânica têm-se mostrado muito benéficos devendo a entubação e ventilação ser feita com sedoanalgesia, de preferência numa unidade de cuidados intensivos tal como ocorreu no caso clínico apresentado (Erulu et al., 2018;Valenta, 2011). Para o controle das fasciculações que aumentam a saturação de dióxido carbono e hipertermia a sedação com diazepam, midazolam, tiopental e sulfato de magnésio foram igualmente benéficos tal como descreve a literatura (Valenta, 2011). ...
... Em caso de edema agudo do pulmão a administração de manitol e furosemida e a subsequente administração de hidrocortisona e vacina antitetânica têm-se mostrado muito benéficos devendo a entubação e ventilação ser feita com sedoanalgesia, de preferência numa unidade de cuidados intensivos tal como ocorreu no caso clínico apresentado (Erulu et al., 2018;Valenta, 2011). Para o controle das fasciculações que aumentam a saturação de dióxido carbono e hipertermia a sedação com diazepam, midazolam, tiopental e sulfato de magnésio foram igualmente benéficos tal como descreve a literatura (Valenta, 2011). ...
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... The black mamba ( Dendroaspis polylepis) is an aggressive snake associated with many bites in Africa [5,6] . The hallmark feature of the snake is its 'inky' black mouth [7] . The snake may range from olive brown to dark grey in color and may grow to over 400 cm [7] . ...
... The hallmark feature of the snake is its 'inky' black mouth [7] . The snake may range from olive brown to dark grey in color and may grow to over 400 cm [7] . Fig. 1 . ...
... The snake inhabits South and East Africa's savannas, rocky hills and the open woodlands. In Europe and parts of North America, the black mamba is popular among exotic snake handlers [7] . Dendrotoxins, α-neurotoxins and other representatives of the 3-finger family of toxins have been reported as the most toxic fractions of the venom [6] . ...
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... On their part, Harrison and colleagues [5] suggested that antivenoms manufactured by PAN AFRICA, INOSAN Biopharma, and Sanofi Pasteur were not effective against all the medically important snake species in sub-Saharan Africa. In our opinion, it is damning that, for a snake that is native to Africa, recent medical literature on black mamba envenomation in humans is largely from Europe [7][8][9]. ...
... Ironically, most of the recent reports of black mamba bites in medical literature have emanated from outside the continent, mainly involving snake breeders or handlers of exotic snakes. Between 2011 and 2017 there have been reports of black mamba bites in Switzerland, Germany, and the Czech Republic [7][8][9]. Within the continent of Africa, Strover [10], Saunders [11], Blaylock [12], Crisp [13], Hilligan [14], Naidoo [15] and their colleagues have reported on black mamba bites in Zimbabwe (1967,1980,1982), South Africa (1986,1987), and Swaziland (1987). To the best of our knowledge, this is the first documented case report of a confirmed black mamba envenomation in East Africa that was successfully treated. ...
... The clinical presentation may vary markedly owing to the array of toxic proteins that make up the venom. Initially, envenomation may be characterized by little or no swelling or bleeding [1,8,10,15], nausea [17], and conjunctival congestion [11,17]. A few minutes later, the victim may begin to sweat profusely [8,17], hypersalivate [10], vomit [15,17], complain of a strange taste in the mouth, and tingling sensations throughout the body leading to paresthesia and weakness [8,17]. ...
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... Without medical treatment, mamba bites are frequently fatal [1]. As mamba bites are rare in Europe [2][3][4][5] treatment can be challenging, particularly if rapid administration of antivenin fails [6]. We report the case of a Swiss snake breeder who was bitten by a black mamba, report the typical clinical course, and review the management of neurotoxic snake bites. ...
... In France, one victim survived a green mamba bite although administration of antivenin failed [6]. Bites by black mambas have been reported in Germany [3] and in the Czech Republic [4]. To our knowledge, our case is the third registered black mamba bite in Switzerland and the first to be published. ...
... General signs of envenomation may include local pain, nausea, cough, and profuse sweating from sympathetic overstimulation. In severe cases, intubation, mechanical ventilation, and circulatory support may be necessary [4]. ...
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Mambas (genus Dendroaspis ) are among the most feared venomous African snakes. Without medical treatment, mamba bites are frequently fatal. First-aid treatment includes lymphatic retardation with the pressure immobilization technique. Medical management comprises continuous monitoring, securing patency of the airway, ensuring adequate ventilation, symptomatic measures, and administration of specific antivenin. We report an unusual case of a snake breeder bitten by a black mamba in Switzerland, report the clinical course, and review the lifesaving emergency management of mamba bites. This case highlights the importance of early antivenin administration and suggests that emergency and critical care physicians as well as first responders all around the world should be familiar with clinical toxinology of exotic snake bites as well as with the logistics to most rapidly make the specific antivenin available.
... Dendroaspis polylepis snakes, also known as black mambas, inhabit a large portion of the sub-Saharan region and their venom is considered one of the most potent among the animal kingdom. The envenomation may cause hypotension, tachycardia, paresthesia in the superior and inferior members and respiratory failure in their victims [6]. Proteomics studies revealed that the D. polylepis venom is mainly composed by Kunitz-type molecules, which includes mamba dendrotoxins (63%), three finger toxins (31%) and metallopeptidases (3%) [7]. ...
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Background: Proteases play an important role for the proper physiological functions of the most diverse organisms. When unregulated, they are associated with several pathologies. Therefore, proteases have become potential therapeutic targets regarding the search for inhibitors. Snake venoms are complex mixtures of molecules that can feature a variety of functions, including peptidase inhibition. Considering this, the present study reports the purification and characterization of a Kunitz-type peptide present in the Dendroaspis polylepis venom as a simultaneous inhibitor of elastase-1 and cathepsin L. Methods: The low molecular weight pool from D. polylepis venom was fractionated in reverse phase HPLC and all peaks were tested in fluorimetric assays. The selected fraction that presented inhibitory activity over both proteases was submitted to mass spectrometry analysis, and the obtained sequence was determined as a Kunitz-type serine protease inhibitor homolog dendrotoxin I. The molecular docking of the Kunitz peptide on the elastase was carried out in the program Z-DOCK, and the program RosettaDock was used to add hydrogens to the models, which were re-ranked using ZRANK program. Results: The fraction containing the Kunitz molecule presented similar inhibition of both elastase-1 and cathepsin L. This Kunitz-type peptide was characterized as an uncompetitive inhibitor for elastase-1, presenting an inhibition constant (Ki) of 8 μM. The docking analysis led us to synthesize two peptides: PEP1, which was substrate for both elastase-1 and cathepsin L, and PEP2, a 30-mer cyclic peptide, which showed to be a cathepsin L competitive inhibitor, with a Ki of 1.96 µM, and an elastase-1 substrate. Conclusion: This work describes a Kunitz-type peptide toxin presenting inhibitory potential over serine and cysteine proteases, and this could contribute to further understand the envenomation process by D. polylepis. In addition, the PEP2 inhibits the cathepsin L activity with a low inhibition constant.
... These envenomings are not associated with hemolysis or local signs, i.e. swelling, hemorrhage, or necrosis [1,3,5]. Bites from D. polylepis are reported to have a very high fatality rate if the victim is not treated [1,6]. In contrast, timely administration of effective antivenoms or implementation of mechanical ventilation has been shown to prevent death from these envenomings [1,3,7]. ...
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Unlabelled: The venom proteome of the black mamba, Dendroaspis polylepis, from Eastern Africa, was, for the first time, characterized. Forty- different proteins and one nucleoside were identified or assigned to protein families. The most abundant proteins were Kunitz-type proteinase inhibitors, which include the unique mamba venom components 'dendrotoxins', and α-neurotoxins and other representatives of the three-finger toxin family. In addition, the venom contains lower percentages of proteins from other families, including metalloproteinase, hyaluronidase, prokineticin, nerve growth factor, vascular endothelial growth factor, phospholipase A2, 5'-nucleotidase, and phosphodiesterase. Assessment of acute toxicity revealed that the most lethal components were α-neurotoxins and, to a lower extent, dendrotoxins. This venom also contains a relatively high concentration of adenosine, which might contribute to toxicity by influencing the toxin biodistribution. ELISA immunoprofiling and preclinical assessment of neutralization showed that polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization of D. polylepis venom, albeit showing different potencies. Antivenoms had higher antibody titers against α-neurotoxins than against dendrotoxins, and displayed high titers against less toxic proteins of high molecular mass. Our results reveal the complexity of D. polylepis venom, and provide information for the identification of its most relevant toxins to be neutralized by antivenoms. Biological significance: The black mamba, D. polylepis, is one of the most feared snakes in the world, owing to the potency of its venom, the severity and rapid onset of clinical manifestations of envenomings, and its ability to strike fast and repeatedly. The present study reports the first proteomic analysis of this venom. Results revealed a complex venom constituted predominantly by proteins belonging to the Kunitz-type proteinase inhibitor family, which comprises the dendrotoxins, and to α-neurotoxins of the three-finger toxin family. The proteins showing highest acute toxicity were α-neurotoxins, which induce post-synaptic blockade of the neuromuscular junctions, followed by dendrotoxins, which inhibit the voltage-dependent potassium channels. The combination of these two types of toxins in the venom underscores the presence of a dual strategy that results in a highly effective mechanism for prey subduction. This complex toxic arsenal is likely to provide D. polylepis with high trophic versatility. The rapid onset and severity of neurotoxic clinical manifestations in envenomings by D. polylepis demand the rapid administration of effective and safe antivenoms. Preclinical tests showed that an antivenom from South Africa and two antivenoms from India were effective in the neutralization of this venom, albeit differing in their potency. Moreover, ELISA immunoprofiling of these antivenoms against all venom fractions revealed that antivenoms have higher titers against α-neurotoxins than against dendrotoxins, thus underscoring the need to develop improved immunization strategies. The results of this investigation identified the most relevant toxins present in D. polylepis venom, which need to be targeted by antivenoms or other type of inhibitors.
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Unlabelled: Only one natural venomous snake-the adder viper-lives in the central European region and its bite is usually associated only with mild course of envenoming. Cases of envenoming caused by exotic snakes among their breeders are clinically more important. Objective: The aim of this study was to analyze the epidemiological and clinical aspects of registered venomous bites caused by exotic snakes in the Czech Republic over a period of 15 years (1999-2013). Materials and methods: This is an observational case series. Data have been collected retrospectively from a database and medical charts of the Toxinology Center belonging to the General University Hospital in Prague. Results: In total, 87 cases of exotic snakebites caused by 34 venomous snake species were registered during the study period, coming from 18 genera of Elapinae, Viperinae, and Crotalinae subfamilies. In the cohort, 29 patients (33.3%) developed systemic envenoming and 17 (19.5%) were treated with antivenom. Ten cases of envenoming (11.5%) were considered as potentially life threatening. No patient died due to envenoming caused by exotic snake bites during the study period. Four illustrative cases of envenoming (Echis pyramidum, Dendroaspis polylepis, Protobothrops mangshanensis, and Proatheris superciliaris) are described in detail. Conclusion: Bites caused by exotic snakes resulted in serious and life-threatening envenomings in some patients. Early transfer to the Center, antivenom administration, and support of failing organ functions contributed to favorable outcome of victims.
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(full pdf version can be downloaded from "Supplementary Resources": right hand column) Two toxins that are potent inhibitors of acetylcholinesterase have been isolated from the venom of the green mamba, Dendroaspis angusticeps. The toxins have been called fasciculins since after injection into mice (i.p. 0.5-3 micrograms/g body weight) they cause severe, generalized and long-lasting (5-7 h) fasciculations. Homogenates of diaphragm, tibialis anterior and gastrocnemius muscles from mice injected with fasciculins showed a decrease in acetylcholinesterase activity by 45-60% compared to muscles from control animals. Histochemical staining revealed a greatly reduced acetylcholinesterase activity at neuromuscular junctions. Fasciculins have 61 amino acid residues and four disulfides. The molecular weights are 6765 (fasciculin 1) and 6735 (fasciculin 2). The sequences of the two toxins differ probably only at one position by a replacement of Tyr with Asp/Asn. 1 g of venom contained about 40 mg of fasciculins, 2/3 of which was fasciculin 2. A similar inhibitor has also been isolated from D. polylepis (black mamba) venom. The sequence of fasciculin 2 is known. Most of the positive charges are concentrated in a small section of the central part of the molecule, and most of the negative charges are in the C-terminal region. Fasciculins appear to have a pronounced dipole character. Fasciculin binds to the peripheral anionic site, since it can displace propidium, a probe for that site, from acetylcholinesterase. In vitro, in Krebs-Henseleit solution containing 2 mM NaH2PO4 (pH 7.4), fasciculin 2 inhibits acetylcholinesterase from human erythrocytes (Ki = 1.1 X 10(-10) M, 37 degrees C), rat muscle (Ki = 1.2 X 10(-10) M, 37 degrees C) and Electrophorus electricus (Ki = 3.0 X 10(-10) M, 22 degrees C). (ABSTRACT TRUNCATED AT 250 WORDS)
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This is a comprehensive monograph on the problems of intoxication incurred by snake venom. This publication is primarily intended for those at all levels of health care, for members of rescue teams, surgeries and emergency hospitals, as well as specialized workplaces and intensive care units. Providing didactic instructions for first aid and treatment procedures, information is also presented on venomous snakes, the fundaments of their morphology and behavior, snakebite prevention, the composition of snake venom, symptoms of envenoming, plus first aid in the event of snakebite for non-professionals, travelers, terrain biologists, and breeders. This book features an updated alphabetical list of types and sub-types of all venomous snakes, including their home ranges, as well as a comprehensive index, list of abbreviations, glossary, and color picture insert with one hundred photographs of venomous snakes.
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The venom of the green mamba, Dendroaspis angusticeps has previously been shown to produce neuromuscular facilitation by increasing acetylcholine release. After gel filtration and ion-exchange chromatography of the whole venom, a basic polypeptide with facilitatory actions was isolated. This polypeptide, named dendrotoxin, has 59 amino acid residues, probably with only 3 disulphide bonds and a blocked N-terminus. When injected into conscious mice, dendrotoxin made the mice hypersensitive to external stimuli and subsequently produced respiratory paralysis. When tested on the isolated chick biventer cervicis nerve-muscle preparation, concentrations of dendrotoxin of 0.5 μg/ml (7×10−8 M) and greater, increased responses to indirect stimulation by 200–250%, without any increase in responses to submaximal concentrations of exogeneous acetylcholine, carbachol, KCl or direct stimulation. The augmentation was slow to develop, not reversed by washing, and could last several hours before slowly waning. Dendrotoxin did not produce spontaneous twitching or contractures. It is concluded that dendrotoxin is not an anticholinesterase, does not affect receptor sensitivity or muscle contractility, but produces twitch augmentation by increasing the amount of acetylcholine released by nerve stimulation. Thus, dendrotoxin appears to represent a snake venom neurotoxin with unusual chemical and pharmacological properties.
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The clinical features of confirmed cases of black mamba snakebites in a 14-month-old child and a 34-year-old man are presented. The steps taken in management are described and reviewed. The importance of early aggressive treatment and general principles of mamba bite management are discussed. To date there has been no reported case of confirmed and medically treated black mamba bite in a child so young.