Terrestrial venomous snakes and snakebites in the Arab countries of the Middle East

Journal Pre-proof Terrestrial venomous snakes and snakebites in the Arab countries of the Middle East Zuhair S. Amr, Mohammad A. Abu Baker, David A. Warrell

PII:

S0041-0101(20)30020-9

DOI:

https://doi.org/10.1016/j.toxicon.2020.01.012

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TOXCON 6275

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Toxicon

Received Date: 5 November 2019 Revised Date:

16 January 2020

Accepted Date: 22 January 2020

Please cite this article as: Amr, Z.S., Abu Baker, M.A., Warrell, D.A., Terrestrial venomous snakes and snakebites in the Arab countries of the Middle East, Toxicon (2020), doi: https://doi.org/10.1016/ j.toxicon.2020.01.012. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Ltd.

Terrestrial venomous snakes and snakebites in the Arab countries of the Middle East Zuhair S. Amra, Mohammad A. Abu Bakerb, David A. Warrellc a Biology Department, Jordan University for Science and Technology, Irbid, Jordan b Department of Biological Sciences, The University of Jordan, Amman, Jordan c Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK ABSTRACT The 12 Arab countries of the Middle East are inhabited by 21 species of terrestrial venomous snakes of varying medical importance. This review considers these species, consisting of 16 viperids, 3 elapids and 2 atractaspidines. Iraq, Jordan, Lebanon, Oman, Saudi Arabia, and Yemen report the largest numbers of snakebites and envenomings. Accessible literature in English and Arabic on venomous snakes and snakebites and available antivenoms is reviewed. Clinical effects include potentially misleading symptoms attributable to anxiety and traditional prehospital treatments. Keywords: Antivenom, Atractaspis, Cerastes, Echis, Middle East, Naja, snakebite, venomous snakes, Viperidae, Walterinnesia

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?Highlights

1. Introduction Geographically, the Middle East includes 12 Arab countries (Bahrain, Iraq, Jordan, Kuwait, Lebanon, Oman, Palestinian Territories, Qatar, Saudi Arabia, Syria, United Arab Emirates, and Yemen) covering the vast area of 3.83 million km2, with about 158 million inhabitants. The area comprises a wide range of habitats, including coastal mountains, forests, semi-arid and arid deserts, with temperate, subtropical and tropical climates (Fig. 1).

Fig. 1. Arab countries of the Middle East . Some 30 species of venomous terrestrial and sea snakes in the Middle East has been emphasized in a number of publications (Turk, 1958; Joger, 1984; Coppola and Hogan, 1992; Leviton et al., 1992; Russell and Campbell, 2015). The most comprehensives studies on the snakes of this region include; Jordan (Amr and Disi, 2011), UEA and Oman (Gardner, 2013), Arabian Peninsula (Gasperetti, 1988; Egan, 2007). Snake bites are a medical concern in all these countries, where many cases are reported annually. The importance of snakebites in the Middle East has been emphasized in a number of publications (Swaroop and Grab, 1954; Warrell, 1995; Chippaux, 1998; Ismail and Memish, 2003; Kasturiratne et al., 2008; Fatani, 2015; Haidar and Deitch, 2015).

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The present study reviews the currently known venomous snakes, snake bite epidemiology, clinical manifestation of snake bites and antivenoms used for treatment in the Arab countries of the Middle East. 2. Venomous snakes Venomous snake systematics is a very important component in understanding the distribution, ecology and epidemiology of snake bites and was addressed in a short-lived series of updates in Toxicon (Wüster et al., 1997). The listed species are based on recent taxonomic reviews (Table 1, Figs. 2-5). For the family Viperidae, Werner et al. (1991) and Werner and Sivan (1992) distinguished Cerastes cerastes from C. gasperettii. The former is distributed in North Africa, into the Negeb desert, Yemen and south west Saudi Arabia (Sindaco et al., 2013). Werner et al. (1999) considered the populations of southwestern Arabia to be Cerastes cerastes hoofieni, and they referred to the hornless population in Wadi Araba in Jordan as Cerastes gasperettii mendelssohni. However, Cerastes gasperettii gasperettii is the subspecies commonly found in eastern and northern Arabia. Babocsay (2003) described the new subspecies, Echis coloratus terraesanctae from the Palestinian Territories and Echis omanensis from Eastern Arabia (Babocsay, 2004). The genus Atractaspis is now included in Lamprophiidae, sub-family Atractaspidinae (Vidal et al., 2008; Pyron et al., 2013; Hillis. 2019; Portillo et al, 2019; Weinstein and Warrell, 2019). The species occurring in the area are A. andersoni and A. engaddensis based on studies undertaken by Trape et al. (2006) and David and Vogel (2010). Trape et al. (2006) considered A. microlepidota to be an African species confined to Senegambia and Mauritania, A. andersoni to be an Arabian species restricted to south western and eastern Arabia, while A. engaddensis is distributed from Israel through Lebanon, Sinai, Jordan to south-western to north-central Saudi Arabia. Table 1 Venomous snakes of Arab countries in the Middle East.







































































3




















Yemen


?






UAE




Syria

Saudi Arabia Qatar

Palestinian Territories

Oman

Lebanon

Kuwait

Jordan

Iraq

Bahrain

Viperidae Bitis arietans (Merrem, 1820) Cerastes cerastes (Linnaeus 1758) Cerastes gasperettii Leviton & Anderson, 1967 Daboia palaestinae (Werner, 1938) Echis borkini Cherlin, 1990 Echis carinatus (Schneider, 1801) Echis carinatus sochureki Stemmler, 1969 Echis coloratus Günther 1878 Echis khosatzkii (Cherlin, 1990) Echis omanensis Babocsay, 2004 Macrovipera lebetina Montivipera bornmuelleri (Werner, 1898) Montivipera raddei kurdistanica (Nilson & Andrén 1986) Montivipera xanthina (Gray, 1849) Pseudocerastes fieldi Schmidt 1930 Pseudocerastes persicus (Duméril, Bibron & Duméril, 1854)


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Elapidae Walterinnesia morgani (Mocquard, 1905) Walterinnesia aegyptia Lataste, 1887 Naja arabica Scortecci, 1932 Lamprophiidae (Atractaspidinae) Atractaspis andersonii Boulenger, 1905 Atractaspis engaddensis Haas, 1950




































Two species of Walterinnesia are now recognised in the Middle East region; W. aegyptia in Palestine, western Saudi Arabia, and Jordan, and W. morgani in Iraq and eastern Arabia (Nilson and Rastegar-Pouyani, 2007). Naja arabica is now regarded as a full species (Trape et al., 2009). Table 1 summarizes the distribution of terrestrial snakes in the Arab countries in the Middle East. The distributional data are based on Joger (1984), Gasperetti (1988), Amr and Disi (2011), and Sindaco et al. (2013).

Fig. 2. A. Bitis arietans from Oman (Photo by V. Víta). B. Cerastes gasperettii from Saudi Arabia (Photo by A. Aloufi). C. Daboia palaestinae from Jordan. D. Montivipera bornmuelleri from Lebanon (Photo by M. Abi-Said).

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Fig. 3. A. Macrovipera lebetina from Jordan. B. Montivipera xanthina (Photo by D. Jablonski). C. Pseudocerastes fieldi from Jordan. D. Pseudocerastes persicus from Iran (photo by Photo by M. Berroneau).

Fig. 4. A. Echis coloratus from Saudi Arabia (Photo by Al Sulimi). B. Echis carinatus sochureki from Oman (Photo by V. Víta). C. Echis khosatzkii from Oman (Photo by R. Sindaco). D. Echis omanensis from Oman (Photo by V. Víta).

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Fig. 5. A. Atractaspis andersoni from Oman (Photo by V. Víta). B. Atractaspis engaddensis from Jordan. C. Walterinnesia aegyptia (Photo by O. Attum). D. Naja arabica from Saudi Arabia (Photo by M. Al Mesheni).

3. Epidemiology and clinical features of snake bites in different Arabian countries 3.1. Bahrain There are five species of terrestrial snakes of which only Forskål’s sand snake (Family Psammophiidae: Psammophis schokari) (“abu khattain”) (Gallagher, 1971) is regarded by some as being capable of inflicting harmful bites http://snakedatabase.org/species/psammophis/schokari. There is no reliable documentation of this claim, but other African species in this genus can cause minimal local envenoming (Weinstein et al., 2011).). 3.2. Iraq Between 1917 and 1924, the Iraq Health Service believed that venomous snakes and snakebites were rare. A fatal case of Echis carinatus envenoming at (Imam) Hamza on the Middle Euphrates in 1923 was the first of several cases recorded in Diwaniyah in 1924 and 1929 (Sinderson, 1924; Corkill, 1932-3). Corkill (1932 and 1933) stated that no casualties from snakebite had been recorded, and that deaths were rare in Iraq in the 1930s. Only eleven cases were traceable in the previous fifteen years. In the Hammar Marshes of SE Iraq, Thesiger (1964) came across only one case of snake-bite during his travels there in the 1950s. A 14-year-old girl was bitten on the foot while stepping into a canoe near Kubaish. She died within 30 minutes. Her face had become almost black from bruising and she had bled from her mouth and nose. This case is difficult to attribute since it seems an unlikely habitat for Echis, Cerastes or Pseudocerastes while M. lebetina occurs only NE of Baghdad. However, 308 snakebite victims were reported between 2002 and 2011 in ThiQar District, which embraces the Marshes (Table 2). There were 22 deaths (mortality 7.1%). 254 patients experienced bleeding. There were slightly more male than female victims (164 M and 144 F). 192 bites were in the lower, and 116 in the upper limbs. Cases were attributed to Echis carinatus (Al-Hammami et al., 2012). 6

In Diwaniyah District, during 2005-2009, 49 patients were reported, 29 males and 20 females. 36.7% were children less than five years old, who suffered 28.6% mortality. 53% of bites were on feet and legs. 83.7% occurred between April and August (Al-Shamsi et al., 2014). Lauer et al. (2011) described neurotoxic effects associated with a bite by Walterinnesia morgani, in a soldier stationed in Iraq. He showed severe weakness, respiratory distress, paraesthesiae around the wound and diplopia. Table 2 Summary of clinical features and mortality of snake bites in Iraq. Year

Region

2002-2011 2005-2009

Thi –Qar Diwaniyah

No. of cases 308 49

No. of deaths 22 14

Clinical effects

Reference

Bleeding Local swelling and edema, pain and irritability, bleeding tendency, anaemia, disturbed level of consciousness, hypotension and shock.

Al-Hammami et al. (2012) Al-Shamsi et al. (2014)

3.3. Jordan Several studies addressed the epidemiology of snake bite in Jordan. The earliest record of snakebites in Jordan was documented by Swaroop and Grab (1954). They reported a total of 84 recorded deaths from snakebite in the 5-year period (1948–1952) without mentioning the total number of cases. Almost half a decade later, Amr and Amr (1983) conducted a retrospective study on snakebites reported by the Ministry of Health during 1970–1972 and 1975–1980, with a total of 112 cases, including seven fatalities. Another study by Disi et al. (1988b) documented 65 cases of snakebites during 1982–1986. Jaghbir and Khoury (1989) examined records of snakebites in Balqa Governorate with a total of 20 confirmed cases. Amr et al. (1994b) presented an epidemiological study on snakebite cases reported during 1982–1992, with a total of 99 cases (Table 3). The previous authors believed that the actual numbers of snakebites were much higher than the above figures, since snakebites were treated with folklore medications and snakebites in remote areas and involving military personnel were not included in the official records. Al Shamari (2002) presented a retrospective study on snakebites in the Ghor es-Safi, southern Jordan Valley. He reported a total of 60 cases admitted to the emergency department at Ghor Safi Hospital. The ages of victims ranged between 46 and 50 years, with 9:1 male to female ratio. Severe cases constituted 12 %. Snakebite data were obtained from Princess Haya Hospital (PHH) in Aqaba, southern Jordan, from 2004 to 2012 (21 cases), from the National Drug and Poison Information Center (NDPIC), Jordan University Hospital covering the years 2009–2012 (15 cases), and from records of the Ministry of Health, Directorate of Environmental Health (DEH) from 2006 to 2012 (34 cases). Of the total snakebites (70 cases), only one case of death occurred in Ajlune (55-year-old male). We witnessed two cases of snakebites caused by D. palaestinae that resulted in death in As Salt Hospital. Neither case was included among the cases documented by the MOH, as data obtained from the NDPIC showed that 13 out of 15 snakebite cases occurred outdoors, while only two cases occurred at patients’ residences. Two, four, and nine patients showed minor, moderate, and severe symptoms, respectively. Snakebites were more common among males compared to females. Males, especially farmers, are more exposed to snakes due to their activity outdoors. According to the records (1982–1986), 72.3 % of snakebites occurred in males and 27.7 % in females (Disi et al., 1988b). In Balqa Governorate, they were almost twice as common among males (Jaghbir and Khoury, 1989). The ages of only 51 patients were obtained. Children 7

and young adults were at highest risk and constituted about 55 % of the total number of cases. People older than 20 years were most affected (Jaghbir and Khoury, 1989). The foot and ankle were most often bitten, followed by finger and hand (Jaghbir and Khoury, 1989). Jaghbir and Khoury (1989) found that most snakebites occurred in April. Amr et al. (1994a) reported similar findings, the lowest incidence being in November. This suggests that snakes become more active during the spring as they emerge in March after hibernation. Table 3 gives a summary of snake bites in Jordan. Table 3 Summary of clinical features and mortality of snake bites in Jordan. Year

No. of cases ? 112

No. of death 84 7

1982–1986 1982–1992 1986 2001

65 99 20 1

0 5 0 0

2001 2004-2012

60 72

0 3

1948–1952 1970–1972 1975–1980

&

Clinical effects

Reference

Not mentioned hypofibrinogenaemia of 90 mg/dl (normal 150–300 mg/dl). blood transfusions was required. Not mentioned Not mentioned Not mentioned Swelling, ecchymoses, severe retrosternal chest pain, nausea and vomiting. Electrocardiogram showed a pattern of acute inferior myocardial infarction.

Swaroop and Grab (1954) Amr and Amr (1983)

Disi et al. (1988b) Amr et al. (1994b) Jaghbir and Khoury (1989) Saadeh (2001)

Al Shamari (2002) Amr and Disi (2015)

3.4. Kuwait There are two reports of snake bites in Kuwait. Mylrea (1928) reported a bite on the foot by a “small brown desert snake” that caused severe pain, shock and incessant vomiting, and, within 24 h, complete left hemiparesis. Within 28 days the victim made a complete recovery apart from residual left ptosis. This suggests a right cerebral hemisphere bleed caused by Cerastes gasperettii (Schneemann et al., 2004). Mylrea (1928) stated that snakebite was uncommon in Kuwait but that very occasionally he had heard instances of sudden death following snakebite. Another case of snake bite resulted from the bite of a king cobra that had been imported from Thailand (Al Tarrah et al., 2009). 3.5. Lebanon Little is known about the epidemiology of snakebite in Lebanon. The report, by Attar and Nassif (1953), provided no local information. A recent study reported 24 cases of snakebite admitted between 2000 and 2014 from Beirut and its suburb Baabdaat. Mean age was 34.6 (±16.4) years. 58.3% of recorded cases were among males. Only one patient brought the snake responsible, a Daboia palaestinae. Systemic signs included tachycardia (33.3%), hypotension (20.8%), anaphylaxis (12.5%) (explained by an antivenom reaction in only one case), headache (4.2%), nausea, vomiting and abdominal pain (4.2% each). Hematological abnormalities included leukocytosis (37.5%), coagulopathy and thrombocytopenia (12.5% each). Four patients had dizziness or impaired consciousness. Complications included “compartment syndrome” treated by fasciotomy, deep vein thrombosis, coagulopathy, acute respiratory distress syndrome, sepsis, congestive heart failure, cellulitis, upper gastrointestinal bleeding, and vaginal bleeding. Most cases were attributed to M. lebetina and D. palaestinae (El Zahran et al., 2018).

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3.6. Oman There are brief reports of snake bites at Ibra Hospital in NE Oman (Pawar, 1985) and in Dhahira region of NW Oman (Bughio, 1997). At the Royal Hospital in Muscat, 65 snake bite cases were reported from May 2006 to August 2008, but in no instance was the snake identified. Males were more often affected than females (90% M and 10% F). Lower (60%) and upper (38%) limbs were involved. Most cases occurred in the evening (60%). The main symptoms were local pain, swelling at the site of the bite without blistering or necrosis, bleeding (5 cases), headache and vomiting. One was shocked. 34 (52%) had an abnormal coagulation profile. Only 47 of the cases were admitted to hospital. One developed acute kidney injury (AKI) requiring renal replacement therapy (Al-Lawati et al., 2009). Table 4 Summary of clinical features and mortality of snake bites in Oman. Year 1995-1996 2006-2008

No. of cases 129 65

No. of death 2 0

2011-2016

83

0

Clinical effects

Reference

? Local pain and swelling, coagulopathy, bleeding, shock, AKI Acute kidney injury, chronic kidney disease

Essein et al. 1997 Al-Lawati et al. (2009)

Khan et al. (2017)

Between 2011 and 2016, 83 cases of snakebite were reported from Ibri in NW Oman (Khan et al., 2017). 84.3% of the victims were male and 53% of the bites occurred in farm areas. In 55.4% and 43.4% the bites were in the lower and upper limbs respectively. Most bites occurred between May and October, with a maximum peak in May (16.9%) and August (18.1%). None of the snakes was identified, but the one illustrated in the paper is E. omanenesis. Table 4 gives a summary for snake bites in Oman. Scrimgeour et al. (2001) mention that 50 or more patients present each year at Rustaq Hospital in the North, but only 24 to the Sultan Qaboos University Hospital, Muscat with one fatality from 1996-2000, but speculated that several hundred might be admitted countrywide each year but with apparently few fatalities. The Omani Ministry of Health, Directorate General of Health Affairs, issued National guidelines on poisoning management in 2006 (http://www.deohoman.org/PDF/Poison/Cover%20layout.pdf ). 3.7. Palestinian Territories An early report by Flower (1933 p834-5), mentioned that a specimen of Echis coloratus collected in “Palestine” (the Jordan Valley) in 1918 by PH Manson-Bahr had killed 3 people. A total of 365 cases of snake bites were recorded between 2008-2010 & 2013-2015 (Albaba, 2017). No details on the seasonality or symptoms associated with snake bites are included in this study. 3.8. Qatar No data are available on the epidemiology of snakebites in Qatar, but there are said to be one or two cases each year presenting at hospitals. Cerastes gasperettii is said to occur in Irkaya game reserve (see http://www.enature.qa/sanctuaries/irkaya/ ). 3.9. Saudi Arabia There are several reviews of the venomous snakes and snakebites Saudi Arabia, yet these lack any original epidemiological or clinical data (Ismail and Memish, 2003; Warrell, 1993; AlAsmari and Debboun, 2013). 9

Al Harbi (1999) compared clinical symptoms in children and adult snakebite victims. He concluded that children showed more serious local and systemic complications than adults, which indicates the need to use a higher dose of antivenom for treatment of children. Malik (1995) found that in Asir, the snake species that were killed by snakebite victims were Echis coloratus (10 out of 15) and a mildly venomous species Platyceps rhodorachis (5 out of 15). In Riyadh, among 28 adult cases of snakebite, 10 brought the dead snake. Seven were Cerastes gasperettii, 1 Echis coloratus, 1 Bitis arietans (although this species does not occur anywhere near Riyadh) and 1 imported American rattlesnake that bit a poison center staff member who was holding it (Al-Durihim et al., 2010). Perry (1988) reported redness, lymphangitis, swelling and local numbness caused by a bite by Jan’s cliff racer (Platyceps rhodorachis) in Israel. Records of unusual complications were recorded among Saudi snakebite victims. Left cerebral infarction was observed in a 13-year old female due to a bite by Echis carinatus (Bashir and Jinkins, 1985). Kingston (1981) reported a fatal case of snake bite attributed to Echis carinatus. He suggested a protocol for snakebite management in Saudi Arabian hospitals. Annobil (1993) examined seven Saudi children who were bitten by Echis coloratus. All exhibited severe signs of swelling, ecchymosis, and blisters, while one patient showed local necrosis and another developed AKI. Al-Homrany (1996) reported on AKI following a bite by E. coloratus, which was later improved with daily hemodialysis. Al-Sadoon and Abdo (1991) reported a fatal case of Atractaspis microlepidota envenoming. The patient received non-specific Pasteur anti Bitis, Echis-Naja venom serum. One case of death was reported by Saddique (2001) in a patient who presented 24 hours after a snake bite. Al-Sadoon (2015) reviewed 1019 cases of snakebites in Riyadh area during 2005-2010. 81.7% of the victims were males, 51.5% of the patients aged 11–30 years, with peak of bites occurred during August. He attributed most cases to Cerastes gasperettii bites. Table 5 gives a summary for snake bites in Saudi Arabia. Table 5 Summary of clinical features and mortality of snake bites in Saudi Arabia. Year

No. of deaths 1

Province

Clinical effects

Reference

1983–1989

No. of cases 82

Al-Baha

1985–1990

21

0

Riyadh

Al-Mohareb and AlSadoon (1994) Fahad and Mohamed (1992)

1986-1988

131

3

Riyadh

1986–2005

21

1

Riyadh

1989–1992

132

0

Asir

1992-1995

66

0

Bisha

1996-1998

70

2

Hail

Coagulopathy, leukocytosis, local complication, and neurotoxicity. Renal impairment, Coagulopathy, leukocytosis, and local complication, Hemiplegia, left-sided cerebrovascular infarction, AKI, pulmonary infarction, and cardiorespiratory failure. Compartment syndrome, amputation of the bitten finger, haematuria, proteinuria, and rhabdomyolysis. Local swelling, pain, redness, coagulopathy and minor bleeding Necrosis, local pain at the site of the bite, swelling, leukocytosis, elevated creatine kinase. Hypertension, hypotension, pallor, restlessness, sweating, vomiting

10

Al-Sadoon and Jarar (1994)

Al-Durihim et al. (2010)

Malik (1995) Al Harbi (1999)

Mahaba (2000)

2005–2010

1019

4

Riyadh

Not included

Al-Sadoon (2015)

3.10. Syria Surprisingly, in a country as large as Syria and inhabited by at least seven venomous species, there are no available documented reports. 3.11. United Arab Emirates A case of snake bite in a 12 years old Emirati boy was published by Al-Hashaykeh et al. (2011). It was claimed that the bite was due to Cerastes vipera (= Cerastes gasperettii). The patient’s condition deteriorated 24 hours after the bite and he developed disseminated intravascular coagulation (DIC) and compartment syndrome despite treatment with National Antivenom and Vaccine Center, Riyadh polyvalent snake antivenom (PSA). After three days, a second dose of PSA resulted in correction of coagulopathy and improvement. A study on of snakebites from Al-Ain, United Arab Emirates (UAE) and Buraimi, Sultanate of Oman reported a total of 62 cases. 87.5% of bites were in males. Feet and hands were the most affected. Major clinical features were pain, local swelling, and coagulopathy, blistering and skin peeling, with few cases of major complications such as; extensive skin peeling, multi-organ failure and compartment syndrome (Alkaabi et al., 2011). 3.12. Yemen Al-Rohani (2004; 2011) reported that 3.4% of cases of AKI in Hudaidah and 1% in Sana’a were due to snakebites. Abohassan et al. (2012) presented clinical complications and outcomes for 50 cases admitted to Al-Salam Hospital at Sa’dah, in N Yemen, after administration of polyvalent snake antivenom. 68% of the cases occurred at night when 84% of the patients were bitten while walking barefooted (44 in lower limbs and 6 cases in upper limbs). Most cases were reported in June and July (27 cases), with sex ratio of 1 female: 4 male. Deaths occurred due to cerebral hemorrhage and multi organ failure. Haidar et al. (2012) reported on 186 cases admitted to hospitals in Hajjah district. The highest number of cases was recorded in July to October. 73.3% of cases were in males. Lower limbs were most affected. At the main government hospital in Taizz in the SW highlands, there were 1-2 cases of snake-bite each week with about one envenomed case every two weeks and occasional fatalities in 2009-11 (Brendan Webb, personal communication).. Table 6 gives a summary of snake bites in Yemen. Table 6 Summary of clinical features and mortality of snake bites in Yemen. Region

% Mortality

Clinical effects

Reference

Sa’dah

No. of cases 50

4

Hajjah

186

3.7

Pain, limb swelling, coagulation abnormalities, cerebral hemorrhage Local swelling, redness, Abnormal coagulation, Anemia, leukocytosis, leucopenia and thrombocytopenia

Abohassan et al. (2012) Haidar et al. (2012)

4 Antivenoms and their availability in the Arab countries of the Middle East 4.1. Iraq Favirept, manufactured by Sanofi Pasteur, France, was the antivenom used by Al-Shamsi et al. (2014). This was specific for mostly North African snakes (Bitis arietans, Cerastes cerastes, 11

Echis leucogaster, Macrovipera deserti, Naja haje, and Naja nigricollis), but is no longer manufactured. Recommended alternative: Razi Vaccine and Serum Research Institute, Iran: equine pentavalent and hexavalent snake antivenom F(abʹ)2 immunoglobulins raised against venoms of Macrovipera lebetina obtusa, Echis carinatus sochureki, Pseudocerastes persicus, Montivipera latifii, M. raddei and Gloydius halys caucasicus http://www.rvsri.ac.ir/Portal/home/?240649/products contact: International Relations, Akram Zand, Razi Vaccine & Serum Research Institute, PO Box 31975/148 Karaj, Hessarak, Alborz, Iran. Telephone +9826 34581009, website www.rvsri.ac.ir email [email protected] 4.2. Jordan Antivenoms were manufactured by Pasteur Institute for Bitis, Echis, and Naja (Ipser Africa), but are no longer produced. However, none of the snakes whose venoms were used to raise this antivenom are present in Jordan. The other antivenom was Behringwerke (Near and Middle East), but among the snakes whose venom it covered, only Cerastes gasperettii occurred in Jordan (Disi et al., 1988b). This antivenom ceased production in the 1980s. Disi et al. (1988b) indicated that both imported antivenoms were inefficient in protecting against most of the snakebites in Jordan, because of venom variations in different species of vipers and even within the same species over their wide ranges of distribution. For the past few years, the Royal Medical Services and the Ministry of Health have used Biosnake snake venom antitoxin manufactured in India, in the unlikely hope of paraspecific activity against venoms of Jordanian W. aegyptia, E. carinatus, M. lebetina and D. palaestinae. Recommended alternative: for Daboia palaestinae envenoming Felsenstein Medical Research Center (previously Rogov) monospecific equine whole IgG Daboia palaestinae antivenom, now manufactured by Kamada, Beit-Kama, 2 Holzman St, Science Park, P.O Box 4081, Rehovot 7670402, Israel contact: Tel: +972 8 9406472 Fax: +972 8 9406473 For other species, either: National Antivenom and Vaccine Production Center, National Guard Health Affairs, Saudi Arabia Polyvalent Snake Antivenom – (Equine) antivenom raised against venoms of Bitis arietans, Echis coloratus, Echis carinatus, Naja haje (N. arabica), Cerastes cerastes, Walterinnesia aegyptia http://www.antivenom-center.com/ contact: [email protected] Telephone +966 11 80 45626, Fax +966 11 252-0188 or: Razi Vaccine and Serum Research Institute polyvalent (see above) 4.3. Lebanon No antivenoms are produced locally. Available polyvalent antivenoms are imported from Syria, manufactured by Syria Scientific Studies and Research Center for D. palaestinae, M. lebetina, Vipera ammonites [Sic] (=Vipera ammodytes), but unlikely to be available currently; and from the National Antivenom and Vaccine Production Center National Guard Health Affairs Saudi Arabia, http://www.antivenom-center.com/ (see above Jordan) 4.4. Oman Previously, inappropriate antivenoms raised against the venoms of non-Omani species were imported from India and France, and, not surprisingly, did not prove effective (Scrimgeour et al., 2001). The currently available antivenom in Oman is manufactured by the National

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Antivenom and Vaccine Production Center, National Guard Health Affairs, Saudi Arabia, (see above Jordan). 4.5. Saudi Arabia Currently, available antivenom in Saudi Arabia is manufactured by the National Antivenom and Vaccine Production Center, National Guard Health Affairs, Saudi Arabia: a polyvalent covering, Bitis arietans, Echis coloratus, Echis carinatus, Naja arabica, Cerastes gasperettii, and Walterinnesia aegyptia and a bivalent covering N. arabica and W. aegyptia. 4.6. Yemen Polyvalent Snake Antivenom_Equine, manufactured by the National Antivenom and Vaccine Production Center, National Guard Health Affairs, Saudi Arabia, (see above Jordan)was administered to patients in the study of Haidar et al. (2012). However, at the main government hospital in Taizz, the only antivenom available was the completely inappropriate imported Indian Snake Venom Antiserum I.P. VINS Bioproducts, Ltd that covers Indian cobra (Naja naja), common Krait (Bungarus caeruleus), Russell's Viper (Daboia russelii) and saw scaled Viper (Echis carinatus), none of which occurs in Yemen ((Brendan Webb, personal communication). 5. Clinical features of snake-bite in the Arabian countries of the Middle East 5.1 Non-specific features 5.1.1. Effects of anxiety and pre-hospital treatment Although snakes were worshipped in ancient times in Mesopotamia and the Arabian Gulf, they are widely feared in modern Arabia, as in most other parts of the world (Gasperetti, 1988). This was exemplified in November 2018, when internet posting of a video of a 2m long Naja arabica in Wadi Dol'ea, Asir, Saudi Arabia, provoked terrified reactions from viewers (https://stepfeed.com/huge-snake-spotted-in-saudi-arabia-and-people-are-terrified-1956). Snake-bite is certainly a frightening experience that can result in a stress reaction unrelated to the direct action of snake venom toxins. Symptoms include tachycardia, tachypnoea, and a sensation of breathlessness or chest tightness that may provoke hyperventilation causing dizziness or syncope, acroparaesthesia and carpo-pedal spasms due to respiratory alkalosis. Accompanying nausea, vomiting and profuse sweating are due to anxiety and sympathetic overactivity. These symptoms are self-limiting and usually resolve spontaneously after reassurance of the victim. However, if they last for longer than a few hours after the bite, they should be considered part of envenoming syndrome. Effects of pre-hospital treatment, such as tourniquets, local incisions and ingestion of emetic herbal remedies may also confuse the clinical picture. 5.2. Effects of envenoming Local pain and swelling at the site of the bite are usually the earliest symptoms suggesting that venom has been injected and the bite is not a “dry bite”, inflicted by a venomous snake without envenoming (Naik, 2017), or a bite by a non-venomous snake or other animal. Paired puncture marks suggest snake fangs, although scorpion or centipede stings, spider, fish or rodent bites, or even punctures by inanimate objects such as thorns or splinters can be misleading. Viper bites cause the most intense local envenoming, often with persistent bleeding and bruising, but N. arabica and Walterinnesia species, and Atractaspis species may also cause swelling, blistering and necrosis, especially if digits (fingers or toes) are involved. Envenoming by any snake may produce tender enlargement of lymph nodes draining the bite site. 13

Systemic effects depend on the species involved (see below). Elapid bites typically cause descending flaccid paralysis. Atractaspidine bites may cause severe cardiovascular disturbances including anaphylaxis and angina pectoris. Viperidae commonly cause shock and haemostatic disturbances resulting in spontaneous systemic bleeding, and sometimes AKI. 5.3. Symptoms of envenoming by particular Middle Eastern species With few exceptions, the clinical literature on snake-bite in Arabia lacks adequate snake identification, making it impossible to distinguish the clinical features of envenoming caused by the different species. Even when the snakes were identified, there was no attempt to relate clinical features to the species responsible (Al-Durihim et al., 2010). In future, it is to be hoped that prospective studies in different countries will be supported by expert identification of the snakes brought by their victims and development of diagnostic immunoassays (Van Dong et al., 2003). Proteomic analysis of venoms might predict likely clinical effects but has not yet been applied to venoms from the Arab countries. Elsewhere, the venom of C. cerastes from North Africa was found to consists of 25-30 toxins, the low-complexity proteome mainly affecting the haemostatic system, consistent with the clinical features described after envenoming by this species in that region (Fahmi et al., 2012). The venom proteome of West African specimens of the B. arietans species complex consists of at least 43 different proteins belonging to nine toxin families, suggesting a wide range of possible clinical effects (Fasoli et al., 2010). 6. Clinical effects of envenoming by different species of snakes of the Arabian Middle East 6. 1. Viperidae 6.1.1. Puff adder, Bitis arietans (Merrem, 1820) No published accounts of puff adder bites in any of the three Arabian countries (Saudi Arabia, Yemen and Oman) where it occurs describe specific symptoms, even in reports of cases where the dead snake was identified (Al-Durihim et al., 2010). In Africa, Bitis arietans may represent a species complex. It is responsible for many serious envenomings throughout the savanna region. Local swelling may be very extensive, commonly involving the entire bitten limb and spreading to the trunk (Warrell et al., 1975). Associated extravasation of plasma causes hypovolaemic shock, a common presenting feature. Local blistering and necrosis may be extensive necessitating debridement and amputation (Figure 6). Arterial thrombosis, compression and ischaemia increase the local tissue damage. Compartment syndromes may develop, especially involving the anterior tibial compartment after bites on the feet and ankles, leading to ischaemic necrosis of intra-compartmental muscles. Myocardial damage and cardiac arrhythmias may contribute to hypotension, a cause of early deaths. There is some regional variation in the pattern of envenoming; spontaneous bleeding, bruising and muco-cutaneous and serosal petechiae associated with thrombocytopenia in West Africa (Warrell et al., 1975), and frank coagulopathy in Uganda (Sezi et al., 1972), South Africa and elsewhere (Lavonas et al., 2002).

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Fig. 6: Clinical symptoms associated with Puff adder, Bitis arietans. A. foot blistering. B. Massive swelling and blistering. C. Necrosis that lead to right lower limb amputation. D. Residual deformity due to lymphoedema.

6.1.2. Arabian (Gasperetti’s) desert horned viper, Cerastes gasperettii Leviton & Anderson, 1967 and Saharan horned viper, Cerastes cerastes Linnaeus, 1758 Cerastes gasperettii is widely distributed in Arabian countries. Bites cause symptoms that are usually mild, involving only local swelling, but in more severe cases, local blistering and necrosis, coagulopathy, bleeding including cerebral haemorrhage and AKI can occur. A few fatal cases caused by the closely related Saharan horned viper (C. cerastes) were reported in the 19th century French colonial military literature. More recently, disseminated intravascular coagulation, microangiopathic haemolysis and acute kidney injury were described in two proven cases of envenoming by C. cerastes (Schneemann et al., 2004) (Figure 7). 15

Fig. 7: Clinical symptoms associated with the Saharan horned viper, Cerastes cerastes. A. Intracerebral haemorrhage. B. Haemoglobin-stained plasma. C. Microangiopathic haemolysis. (Schneemann et al., 2004)

6.1.3. Palestine viper, Daboia palaestinae (Werner, 1938) Large series of bites are reported from Israel, where this species causes 100-300 bites each year (Efrati and Reif, 1953). Within 15-20 minutes after the initial pain of the bite, victims report a sudden sense of weakness, and restlessness, and begin to vomit and sweat. Abdominal pain is associated with diarrhea which may be watery and blood-stained. There is an anaphylactic syndrome: angioedema affects lips and face, the tongue, which may swell to “several times its normal size”, the glottis (requiring tracheostomy in one case); urticaria; tachycardia; hypotension and shock causing collapse and unconsciousness. Spontaneous bleeding affects the skin, soft tissues, muscle, brain, heart muscle, lungs, kidneys and gastrointestinal tract. Rare neurological abnormalities are attributed to cerebral oedema or focal intracranial haemorrhages. Tender, erythematous swelling extends up the bitten limb and onto the trunk. There is local serous or sanguinous blistering, bruising, lymphangitic lines and regional lymphadenopathy. Superficial necrosis may occur at the site of the bite and roofs of blisters exfoliate. Hypovolaemic shock may supervene within a few days in untreated cases. There is progressive anaemia, thrombocytopenia, leucocytosis and haemoconcentration, but the blood usually remains coagulable, although with increased fibrinolysis. Transient proteinuria 16

may occur. Fatalities occur within 2-48 h of the bite, attributed to intractable shock or bleeding. At autopsy, extensive haemorrhages were found in the heart, serous membranes and gastrointestinal and urinary tracts (Efrati and Reif, 1953). Case-fatality in Israel has decreased from 6–10% to 0.5–2% since the introduction of specific antivenom and other improvements in treatment. A retrospective review of bites by this species in children in Israel emphasized the frequency of nausea, vomiting, abdominal pain, tachycardia and hypotension with tense local swelling interpreted as “compartment syndrome” in a few cases. Thrombocytopenia and mild coagulopathy were rare findings (Pivko-Levy et al. 2017). A recent case of D. palaestinae bite in Jordan showed swelling, blistering and haemorrhages (Fig. 8).

Fig. 8. Swelling, blistering and haemorrhages on the shoulder due to a bite by the Palestine viper, Daboia palaestinae.

6.1.4. Saw-scaled/carpet vipers (Echis) This genus of vipers is of enormous medical importance. It is widely distributed in the northern third of Africa from Senegal in the west, to Egypt and the horn of Africa in the east, north to the countries bordering the Mediterranean and south to the Tana River in Kenya. Throughout this range, it is usually the most important cause of human snake bite morbidity and mortality. In Africa, bites are most common in West Africa, where E. ocellatus is the most important species. Echis (ocellatus) romani bites in northern Nigeria: only 4% of patients admitted to the hospital with proven E. ocellatus bite lacked signs of envenoming, the lowest rate of “dry bites” reported in any large case series of snake bites (Warrell and Arnett, 1976; Warrell et al., 1977; Warrell, 1979). The remainder had both local and systemic envenoming. Twelve per cent developed local blistering (Figures 9A and 9C) and 9% necrosis (Figure 9D), sometimes requiring amputation or skin grafting. Local swelling and bruising may be extensive (Figure 9B and 9E). Coagulopathy (attributable to venom prothrombin- and Factor X- activators) was universal, resulting in persistent local bleeding and bleeding from recent wounds (Figure 10A). In 55% of patients there was spontaneous systemic bleeding, usually from the gingival sulci (Figure 10B). Thrombocytopenia (<103 x109/l) was present in only 7%. AKI is very unusual. Most deaths are attributable to intracranial or intra-abdominal haemorrhages.

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Fig. 9. A. Swelling and blistering due to E. ocellatus bite. B. Bruising due to E. ocellatus bite. C. Haemorrhagic blister due to E. ocellatus bite. D. Necrosis due to E. ocellatus bite. E. Swelling and blistering due to E. coloratus bite.

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Fig. 10. A. Local bleeding due to E. ocellatus. B. Bleeding gums due to E. ocellatus bite.

6.1.5. Echis borkini Cherlin, 1990 There are no specific published reports of bites by this species, formerly known as E. pyramidum in SW Saudi Arabia and W Yemen. 6.1.6. Sochurek’s, Stemmler’s or Eastern saw-scaled viper, Echis carinatus sochureki Stemmler, 1969 There are no specific clinical reports from UAE and NE Oman, but frequent and severe envenoming by this sub-species, with case fatalities exceeding 20%, was clearly described in the older literature from Pakistan and NW India. It was recently ‘rediscovered’ in Bikaner, Rajasthan (Kochar et al., 2007), where the large E. c. sochureki [32–80 (average 60) cm in total length] were being misidentified as Russell’s Vipers. In Jammu in northern India, this taxon is the commonest cause of envenoming (Bhat, 1974). In a series of 117 proven cases, all developed systemic envenoming. Pain and swelling started immediately, coagulopathy was detectable within 6 hours of the bite in two-thirds of cases (incoagulable blood in 78 %, defective 19

coagulation in 22 %) and systemic bleeding was detectable within 6–72 hours. Other symptoms included vomiting (38 %), abdominal pain (37 %), regional lymphadenopathy (27 %) and shock (2 %). Sites of bleeding were ecchymoses, haematuria (in the majority), haemoptysis, gums, haematemesis, epistaxis, rectal and intracranial (Figure 11). Although 42 % developed blistering, necrosis did not occur. Three pregnant patients suffered severe bleeding resulting in abortion. Very few patients, including one who died developed AKI.

Fig. 11. Unequal pupils resulting from subdural haemorrhage following Echis carinatus sochureki bite (Courtesy of Dr PD Tanwar).

6.1.7. Painted or Burton’s saw-scaled viper, Echis coloratus Günther 1878 There are reports of some 80 cases from Israel and a few from elsewhere (Benbassat and Shalev, 1993; Warrell and Arnett, 1976). Local pain and swelling are common and, in severe cases, swelling may involve the whole limb and is associated with bruising, haemorrhagic blisters and necrosis in 9% of cases in Israel. Systemic symptoms appear 15-120 minutes after the bite: nausea, vomiting, headache, spontaneous bleeding from gums, nose, gastrointestinal and urinary tracts and recent wounds. Most patients have incoagulable blood, hypofibrinogenaemia and elevated fibrin(ogen) degradation products by the time they are admitted to hospital. About 20% have thrombocytopenia less than 100 x 109/l. A few patients, including one of the reported fatal cases, develop AKI. Anaemia is attributable to microangiopathic haemolysis or haemorrhage. Haemostatic dysfunction persists for up to 9 days unless antivenom is given. Other abnormalities include hypotension, shock, loss of consciousness, Electrocardiogram (ECG) changes, neutrophil leucocytosis, proteinuria and microscopic haematuria with casts. In two cases, histopathological changes suggested “acute haematogenous interstitial nephritis”, focal mesangial proliferation and tubular necrosis. Only four fatalities have been reported. Compared to envenoming by other Echis species, E. coloratus seems to be more likely to cause thrombocytopenia and AKI but the case fatality is lower. 6.1.8. Dhofar carpet viper, Echis khosatzkii (Cherlin, 1990) No bites have been reported by this small species from E Yemen and SW Oman. 6.1.9. Oman saw-scaled viper, Echis omanensis Babocsay, 2004 20

In a single case reported from Oman, there was severe pain and rapidly progressive local swelling but no evidence of systemic envenoming. (Al Hatali et al., 2015). 6.1.10. Levantine or snub-nosed viper, Macrovipera lebetina (Linnaeus 1758) According to WHO (2018), this species is of the highest (category 1) or secondary (category 2) medical importance in four Arab countries (Iraq, Jordan, Lebanon and Syria), and in 11 other countries i. It is generally regarded as a dangerous species. Swelling may extend to involve the whole bitten limb, and trunk with bruising, lymphangitic markings and regional lymphadenopathy. Necrosis requiring amputation of bitten digits is common (Figure 12). Systemic symptoms include nausea, vomiting, trembling, hypotension, shock, tachycardia, syncope, cold sweats and spontaneous bleeding (haemoptysis, melaena, subconjunctival haemorrhages). Anaemia, with evidence of haemolysis, thrombocytopenia, and leukocytosis were observed. In Iraq, it was considered the most important cause of snake-bite casualties with 50% case –fatality. Fatal cases have been reported in Cyprus and Soviet Union (Warrell, 1995). Clinical symptoms develop soon after the bite. Severe pain, swelling, and bruising with lymphangitic lines and painful regional lymphadenopathy may spread rapidly to involve the whole bitten limb and trunk. Sero-sanguinous blisters may appear preceding local necrosis that may require surgical debridement or amputation. Systemic symptoms include, nausea, vomiting, diarrhea, fever, rigors and trembling. Falling blood pressure and tachycardia can progress to shock. Coagulopathy and thrombocytopenia may lead to extensive ecchymoses, sub-conjunctival and retinal haemorrhages, haemoptysis and melaena, resulting in severe anemia. Acute kidney injury appears uncommon. Unfortunately, no detailed accounts of its clinical effects have been documented in the Arab region, but the following cases have been reported elsewhere. In Haifa, Israel, where this species may now be extinct, a 40-year-old man was bitten in the leg in 1954. On admission, he was in severe shock (blood pressure 60/40 mmHg) with nausea, vomiting, a rapid weak pulse, and melaena. Over the next 24h, blood-filled blisters developed in the bitten leg, with swelling and ecchymoses involving the whole limb, abdomen up to the umbilicus and back. He became profoundly anaemic and thrombocytopenic without coagulopathy but gradually began to recover. However, on the 6th day post-bite, he developed bilateral optic neuritis and blindness associated to retinal haemorrhages (Guttmann-Friedmann, 1956).

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Fig. 12. Swollen pre-necrotic finger due to Macrovipera lebetina bite.

In Cyprus, a M. l. lebetina (“koufi” or deaf snake) bit a shepherd on his scalp while he was drinking from a forest pool. He was admitted 8 h later semi-conscious, in great pain and with swelling of the face, scalp, neck, fauces (oropharyngeal isthmus), soft palate, and upper chest. He was feverish and shocked, and coughed up blood and mucus. He had ecchymoses of the eyelids, subconjunctivae and one side of his abdomen with swelling and bruising of the penis and scrotum (Fraser, 1929). A 40-year-old man was bitten on his right index finger by a 75 cm long specimen from northern Cyprus. Swelling and severe pain progressed half way up his right arm within 3 hrs. After 2½ h he developed hypotension, uncontrolled movements of arms and legs and he felt faint with dyspnoea, tachycardia, sweating and trembling which disappeared spontaneously after 20 minutes. There was no coagulopathy. He recovered with a small scar on the finger (Gocmen et al., 2006). In Jammu and Kashmir, Northern India, bites by M. l. cernovi (“gûnas”) were believed to be generally fatal (Fenton, 1909). A soldier was bitten on the finger by a 94.5 cm long M. l. cernovi while sleeping in a cot at an altitude of 7800 feet (2380m). Swelling and bruising extended to involve the entire bitten arm and shoulder and he had mild hypotension, neutrophil leucocytosis and thrombocytopenia without coagulopathy. The bitten finger became necrotic and was amputated (Sharma et al., 2008). In Srinagar, a man was bitten on his penis while urinating in an open field, but developed only local swelling, necrosis at the fang punctures and mild coagulopathy (Hussain and Jan, 2015). 6.1.11. Lebanon viper, Montivipera bornmuelleri (Werner, 1898) No bites by this rare species from Lebanon, Israel and Syria have been reported. 6.1.12. Caucasus or Radde’s viper, Montivipera raddei kurdistanica (Nilson and Andrén, 1986) Darevsky (1966) described fatal envenoming in Armenia 12 hours after a bite. 22

6.1.13. Ottoman or Coastal viper, Montivipera xanthina (Gray, 1849) No detailed account of envenoming by this species has been published. The Turkish literature fails to distinguish effects of bites from other native vipers. 6.1.14. Field’s and Persian horned vipers, Pseudocerastes fieldi Schmidt 1930 and Pseudocerastes persicus (Duméril, Bibron and Duméril, 1854) In Iran, the most common clinical manifestations of envenoming are localized pain and swelling, associated with necrosis (gangrene) of the limb. Venom spreads through the superficial lymphatic vessels, causing severe pain and swelling in its path, sometimes with ulceration, oedema and superficial thromboses that slowly spread. Reports from outside Iran (e.g. in Israel) describe only local envenoming. 6.2. Elapidae 6.2.1. Eastern desert black cobra, Walterinnesia morgani (Mocquard, 1905) An Iraqi man bitten by a large black snake in Baghdad developed respiratory distress and generalised limb weakness. At the site of bite there was mild oedema and erythema and later an area of numbness. During recovery, he experienced double vision without objective evidence of external ophthalmoplegia but made a complete recovery (Lauer et al., 2011). 6.2.2. Egyptian or Western desert black cobra, Walterinnesia aegyptia Lataste, 1887 Five patients envenomed in Israel developed local pain and swelling with systemic features that included fever, generalised weakness without specific signs of neurotoxicity, headache, nausea, vomiting and peripheral neutrophil leucocytosis. All recovered in a few days (Yayon et al., 1988; Lifshitz et al., 2003). The close phylogenetic relationship between Walterinnesia and Aspidelaps (Pyron et al. 2013) suggests that envenoming by Walterinnesia might result in classical descending postsynaptic paralysis reported after A. lubricus and A. scutatus bites and perhaps effectiveness of South African Vaccine Producers (SAVP) antivenom (Whiteley et al., 2019). 6.2.3. Arabian cobra, Naja arabica Scortecci, 1932 There are no clinical reports of bites by this species but, envenoming by the related Naja haje in Africa may cause local swelling but without necrosis. Classical neurotoxic symptoms appear as early as 30 minutes after the bite and can evolve to the point of fatal respiratory paralysis within 2-16 hours of the bite (Warrell et al., 1976). There are signs of progressive descending paralysis, starting with bilateral ptosis (Fig. 13), external ophthalmoplegia (causing diplopia – double vision) and weakness of the muscles innervated by the cranial nerves so that the victim cannot open the mouth, clench the jaws, protrude the tongue, swallow, protect the airway from secretions, speak, flex the neck and eventually cannot breathe. When the respiratory muscles become affected the pattern of breathing is initially abdominal or “paradoxical”: the abdomen expands during inspiration due to contraction of the diaphragm. Respiratory distress increases, the patient becomes anxious, sweaty and cyanosed and will die unless ventilated artificially.

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Fig. 13. Neurotoxic envenoming causing bilateral ptosis as might be expected following Naja arabica envenoming.

6.3. Lamprophiidae (Atractaspidinae) 6.3.1. Genus Atractaspis (burrowing asps or stiletto snakes) Atractaspis andersonii Boulenger, 1905 Atractaspis engaddensis Haas, 1950 Four of the species in this genus; A. microlepidota , A. irregularis, A. engaddensis and A. corpulenta have proved capable of killing humans (Weinstein and Warrell, 2019). Local effects include pain, swelling, blistering, necrosis requiring amputation in several published cases (Fig. 14), tender enlargement of local lymph nodes, local numbness or paraesthesiae. The most common systemic symptom is fever. Most of the fatal cases died within 45 minutes of the bite after vomiting, producing profuse saliva and lapsing into coma. Severe envenoming by A. engaddensis (in Israel) may produce violent anaphylactic and autonomic symptoms (nausea, vomiting, abdominal pain, diarrhoea, sweating and profuse salivation) within minutes of the bite. One patient developed severe dyspnoea with acute respiratory failure, one had weakness, impaired consciousness and transient hypertension and in three there were electrocardiographic changes (ST–T changes and prolonged PR interval) (Kurnik et al., 1999). Mild abnormalities of blood coagulation and liver function have been described. Atractaspis venoms contain endothelin-like peptides such as sarafotoxins (A. engaddensis) that can have marked cardiovascular effects. Venoms also contain haemorrhagic and necrotic factors but no true neurotoxins, although the transcriptome of an African A. aterrima venom gland contained a large diversity of potentially neurotoxic three finger toxins of unknown function (Terrat et al., 2013).

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Fig. 14. A. Digital necrosis due to Atractaspis fallax bite. B-D. Extensive necrosis due to Atractaspis engaddensis bite. Acknowledgments Our thanks are extended to Mr. Mohammad Al-Saraireh for providing images for snakebite cases from Jordan. We would like to thank Mounir Abi-Said, Mohammed Al Mesheni, Abdulhadi Aloufi, Omar Attum, Matthieu Berroneau, Daniel Jablonski, Roberto Sindaco and Vojtěch Víta for providing images for venomous snakes. Our gratitude is also extended Qamar Al-Mimi for map preparation.

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Ethical statement This work is a review paper and no human or animal subjects were used in this study

Declaration of interests ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: