Snakebite incidence in the years 2013–2019

Like the absolute number of snakebites, snakebite incidence peaked in the years 2014 (5.55 per 100,000 population), 2015 (6.84) and 2016 (5.50). This temporary increase took place during a slight reduction in the population of the Republic of Cyprus, which was lower between 2014 and 2016 (850,033 on average) compared to the 2013–2019 average of 862,314. At the same time, the mean annual precipitation (2014–2016: 435.6 mm) was lower than the mean precipitation for the 2013–2019 period (475.8 mm). This appears surprising, as rainfall is usually positively correlated with the reproductive activity of venomous snakes, and is of critical importance for agriculture [30]. Consequently, wetter years might have been expected to result in increased farming activities combined with prolonged movements of snakes, resulting in higher encounter rates between people and venomous snakes. The data of the study period suggest that this was not the case in Cyprus: Although the precipitation in 2018 (606.5 mm) and 2019 (796.8 mm) was 27% (2018) and even 67% (2019) above the annual average from 2013 to 2019, snakebite incidence was only 4.22 in 2018 and 3.49 in 2019, which was 12% (27%) below the annual average from 2013 to 2019 (4.79).

It is also noteworthy that the wettest year of the 7-year period (2019) had the second lowest snakebite incidence. However, most of the rainfall of 2019 occurred in December (208.3 mm), a month with generally low levels of snakebite. Still, precipitation during the dry season from June to September was much higher in 2018 (41 mm) and 2019 (43.4 mm) than in 2014 (34.5 mm), 2015 (13.3 mm) and 2016 (12.7 mm), although less snakebites were recorded during the dry season in 2018 (26) and 2019 (21) than during the same period in 2014 (33), 2015 (35) and 2016 (30). Collectively, this suggests the possibility that the more widely distributed availability of water in the summers of those years that received unusually high precipitation might have resulted in a reduced need for snakes (and perhaps also humans) to assemble near the usually few remaining bodies of water, which in turn might have resulted in less frequent encounters between snakes and humans.

Snakebite occurrence over the year

The culmination of snakebite cases in Cyprus during the dry summer season is in line with the frequent observation of M. l. lebetina close to water during this period. As the Cypriot summer proceeds and landscapes dry out, water bodies provide significant advantages for blunt-nosed vipers such as shelter, ambush sites, ease of water uptake, and thermoregulation. Consequently, there is a constant risk for people to encounter M. l. lebetina at water bodies (including swimming pools) during summer [10]. Although blunt-nosed vipers usually hibernate from November to March in Cyprus, they may still be active in winter under favorable weather conditions [2]. This can explain the 22 cases of envenomation recorded between November and March (2013–2019).

Sex ratio, age distribution, length of stay in hospital and snakebite mortality

The highly unequal distribution of snake envenomation incidence among sexes (6.85 per 100,000 population in Cypriot males compared to 2.82 per 100,000 population in Cypriot females) underlines the increased risk of bites by venomous snakes that males face compared to females in Cyprus. An explanation might be that in Cyprus, occupational outdoor activities are possibly more commonly pursued by men, who thus may be more likely to encounter M. l. lebetina. This sex-specific bias is also found in tropical developing countries, where snakebite is considered an occupational disease most commonly affecting young agricultural workers, particularly men [39, 40]. The presence of very young and old age groups as well as women in the snakebite statistics indicates that not only middle-aged people and men are at risk of venomous snakebite on the island. In fact, snakebites in Cyprus also take place in private gardens, where they are more likely to affect people of both sexes and all age groups alike [10]. People of 50 years and older made up 48% of all registered snakebite victims, although accounting for only 32% (2013), 33% (2014, 2015) and 34% (2016–2019) of the Cypriot population, which hints at an increased risk of snakebite faced by these parts of the population. One reason might be the higher representation of older age groups (50+ years) in rural areas with nearby blunt-nosed viper populations. However, on the one hand, the proportion of these age groups did not differ strongly between the rural (32.5%) and urban (30.3%) population of Cyprus in 2011 [41]. On the other hand, there were remarkable differences between the districts of Paphos, Limassol, Nicosia and Larnaca in the proportion of older age groups (50+ years) among the rural and urban populations. While the proportion of 50+ year-old people was almost equally represented in rural and urban areas of Nicosia (30.1% vs 31.0%) and Larnaca district (30.4% vs 29.5%), 50+ year-old people made up a higher proportion in the rural population of Limassol district (35.1% vs 30.3% urban), and were especially dominant among the rural population in Paphos district (45.7% vs 28.8% urban) [41]. Thus, older-aged people in Paphos district are more likely to encounter venomous snakes than in other districts. Interestingly, Paphos is also the district with the highest observed abundance of M. l. lebetina in Cyprus [2], which may contribute to generally higher snake envenomation rates in this district. Furthermore, it can be assumed that traditional outdoor activities (e.g., shepherding, farmwork) are more commonly pursued by older-aged people (own observations), which additionally increases their risk of encountering blunt-nosed vipers. This assumption is supported by the strong representation of the 50–69-year-old, who account for 76% of all snakebite victims over 50, and who are younger and thus more likely to conduct physically demanding outdoor activities than people of 70–89 years of age. With approximately 20% of all envenomations, the age group of 60–69 years is most strongly affected, which could be due to less effective prophylactic measures undertaken against snakebite by people within this age group. An explanation may be that older people in rural areas apply modern outdoor safety measures (e.g., wearing safety gloves and protective boots for farm work) less commonly than younger people, as older persons may show less risk aversion than their younger counterparts [42]. The fact that 84% of all patients spent a relatively short time in hospital (up to 4 days) suggests clinical courses of snake envenomation in Cyprus that are mostly mild and/or uncomplicated. This is further highlighted by the low average number of days spent by snakebite patients in hospital (2.65). However, the median (2 days) would be a more appropriate measure, as most patients (62.5%) stayed in hospital for a maximum of 2 days only, while the relatively small share of patients with a stay of 5 days or more (16%) is responsible for the strong skewness of the distribution to the left. With one directly and another indirectly related death in 288 hospital admitted snakebite cases between 2013 and 2019, the snakebite mortality in the Republic of Cyprus was very low.

Distribution over hospitals

The numbers of snakebite-related public hospital admissions in four major Cypriot district hospitals (2013–2019) do not correlate with the population sizes (2019) of the corresponding districts. While the population size of Paphos district is 95,400 (only 11% of the population of all five districts), 51% of all hospital-admitted snakebite cases in the Republic of Cyprus were registered at Paphos General Hospital alone. On the other hand, Larnaca and Famagusta, with a combined total of 197,900 inhabitants (22% of the population) only had eight cases (3%) of snake envenomation at their two major district hospitals. With 346,400 inhabitants, Nicosia district has a share of 39% of the population, but only 32 people (11% of all cases) were admitted with snake envenomation to the district’s general hospital from 2013 to 2019. In comparison, the recording of 30% of all snakebites (86 cases) at Limassol General Hospital is approximately proportional to the number of Limassol district residents (248,300), which amounts to 28% of the population of all five districts. The registration of slightly more than half of all hospital-admitted snakebite cases only at Paphos General Hospital is notable, as Paphos is also the district with the highest density of M. l. lebetina in Cyprus (see Fig. 8). While the common occurrence of M. l. lebetina in Paphos may hint at an increased risk of snake envenomation in this district, it does not necessarily have to correlate with the number of admissions to Paphos General Hospital, as snakebite victims may be transferred from other districts as well. Connectivity may be an important factor, as Paphos General Hospital can be easily reached from Limassol via the A6 Highway, and from Polis via the B7 country road, and is situated less than 500 m away from the main junction of both roads. Also, as the five district general hospitals are better equipped to manage cases of snake envenomation, snakebite victims may be referred to them from rural hospitals, or directly seek care at secondary or tertiary referral centers. For example, people bitten in the Polis Chrysochous area may prefer to visit Paphos General Hospital, instead of presenting to the nearby hospital in Polis. In fact, the snakebite-related admission numbers in the rural hospitals of Polis and Kyperounta (5% of all cases) are surprisingly low, given that both are situated in areas with common occurrence of M. l. lebetina (see Fig. 8), which hints at the above-mentioned trend. Finally, a possible explanation for the outstandingly high number of snakebite-related admissions to the general hospitals in Paphos and Limassol (together accounting for 81% of all admissions) may be the double-counting of patients, due to the transfer of inpatients from other hospitals (e.g., in Polis). In such a case, a snakebite patient being transferred between two different hospitals will be registered as two different envenomation cases. As the available dataset does not provide the patients’ personal information, there is no mechanism to avoid double-counting, and hence the patient can be easily confused with two different persons (each at another hospital). This may lead to particularly high numbers of registered patients in larger hospitals.

Fig. 8

Distribution of Macrovipera lebetina in Cyprus, shown by red dots (map from Baier et al. 2013 [2]). The location of the seven hospitals in the Republic of Cyprus is shown by yellow stars

Care-seeking behavior of snakebite victims

Since the available dataset of this retrospective study does not include information on the care-seeking behavior of snakebite victims, there is no empirical basis for identifying and discussing the factors that determine their hospital selection preferences (e.g., accessibility, reputation, cost, specialization, superior equipment, number of available beds). However, public hospitals in Cyprus are free of charge for all patients presenting to the emergency department and are also much less costly for in-patients than private hospitals. Hence, these circumstances suggest that at least snakebite victims with a low-to-average income would preferably visit public hospitals. However, no data were available from private hospitals, for inpatients.

Antivenom administration in Cyprus

Since at least 1971, antivenom is given to documented victims of snake envenomation in Cyprus, who present to the emergency department of public hospitals. “Polyvalent Snake Venom Antiserum” produced by the Egyptian Organization for Biological Products & Vaccines (VACSERA, Cairo, Egypt) has been used since at least 2009 to treat snake envenomation in Cyprus (M. Antoniou [Pharmacist at Nicosia General Hospital], pers. comm., 5 November 2020). The polyvalent antivenom from VACSERA is raised against the venoms of several venomous snake species, specifically from Naja haje, N. nigricollis and Cerastes cerastes [43], although its efficiency has not yet been tested by the WHO [44]. According to the manufacturer, it also has paraspecific neutralizing activity against the venoms of several oriental viper species, including M. lebetina [45]. As several antivenoms exist that are raised against the venoms of palaearctic vipers [44, 46], in some cases even specifically against the venoms of M. lebetina subspecies (i.e., monospecific antivenom against M. l. turanica by UzbioPharm (Tashkent, Uzbekistan) [44, 47]), it may be expected that the latter have better neutralizing capacities against M. l. lebetina venoms. Besides the monovalent antivenom from UzbioPharm, polyvalent antivenoms with stated (specific or paraspecific) neutralizing activity against M. lebetina venoms are produced by different manufacturers in addition to VACSERA, including the Institut Pasteur de Tunis (Tunis, Tunisia), the Institut Pasteur d’Algerie (Algiers, Algeria), the Imunološki Zavod (Institute of Immunology, Zagreb, Croatia), the Institute of Virology, Vaccine and Sera TORLAK (Belgrade, Serbia), Inosan Biopharma S.A. (Madrid, Spain), the Razi Vaccine & Serum Research Institute and the Padra Serum Alborz (both in Karaj, Iran), as well as the Vetal Serum ve Biyolojik Ürünler Üretim Sanayi Tic. A. Ş. (Adıyaman, Turkey) [44]. The WHO (2016) furthermore lists the National Institute of Health in Islamabad (Pakistan) among the producers of polyvalent antivenom against M. lebetina venom [48].

Medical importance of M. lebetina

Although M. lebetina has been rated as one of the snake species of highest medical importance (WHO category 1) in Algeria, Iraq, Iran, Lebanon, Syria, Turkey, Armenia, Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan, Tajikistan, Uzbekistan, Turkmenistan and Afghanistan, and as a snake species of secondary medical importance (WHO category 2) in Cyprus, Jordan, Tunisia and Pakistan [49], there clearly is a lack of clinical and epidemiological research on envenomation caused by these widely distributed vipers. While a few published case reports illustrate the range of symptoms and signs that may follow envenomation by this species, most are anecdotal or offer little clinical detail [2, 10, 29, 50]. Fraser [12], Hopkins [51] and Göçmen [52] described bites caused by M. l. lebetina from Cyprus. In the first case, occurring 1929, a shepherd was bitten on the scalp while kneeling down to drink from a forest pool in Cyprus. He was admitted to the hospital in Famagusta (8 h after the bite), and discharged 11 days later. This patient initially suffered from a loss of consciousness, massive edema and partial loss of speech, and his bite and incision wounds healed slowly [12]. Two other bites described by Hopkins (1974) occurred when army personnel from the United Nations Peacekeeping Force in Cyprus (UNFICYP) were bitten on the back of the right hand (first case) and on the calf (second case). In the first case, there was initially swelling and vomiting, followed on the third day by high fever and signs of cellulitis. On the 15th day, the patient reported anesthesia and paralysis of his right arm almost up to his elbow. Paralysis resolved within 5 days and anesthesia within 26 days. In the other case, the patient initially suffered from severe anxiousness and cramps in the injured limb, but was almost free of symptoms on the following day [51]. A particularly severe case was reported by Schweiger (1983) who was bitten by a large (150–160 cm) M. l. obtusa in his right forearm near İskenderun (Turkey) and subsequently suffered massive painful edema of the bitten arm extending to the trunk and other arm, blistering, myonecrosis requiring the amputation of the bitten limb, thrombocytopenia, coagulopathy, haemorrhage, hypovolaemic shock, acute kidney injury, necrosis of the lungs, paraesthesia, complete loss of motor function of the legs, and contractures of the knee joints. Ten months after the bite, the patient had largely regained his ability to walk, albeit with highly reduced leg strength [53]. Göçmen (2006) reported a bite on a 40-year-old male researcher who was bitten into a right-hand finger by a 75-cm-long male Cypriot M. l. lebetina. Five minutes after the bite, edema started to develop and within 3 h advanced to the center of the right arm, accompanied by severe pain. Further symptoms included hypotension, shock, tissue necrosis, hemorrhage, melanoderma, and considerable quantitative differences in the fractions of albumin, globulin and albumin/globulin ratios. After 24 hours, the patient’s condition had normalized, and he was discharged from hospital. Complete recovery took place after the sixth week [52]. Sharma et al. (2008) described a case from Jammu and Kashmir, in which a 33-year-old male soldier resting in his bed was bitten in his left hand by a 94.5 cm long M. l. cernovi. Twelve days after the bite, the bitten finger had become necrotic and was amputated [54]. In another case in Kashmir, a 46-year-old farmer suffered a M. lebetina bite to his penis while urinating on an open field [55]. In both cases, the main symptoms of envenomation included edema, bruising and necrosis around the bite site. The second case in addition had mild coagulopathy but overall a milder clinical course and was discharged 36 hours after the start of treatment. Kazemi et al. (2019) presented five cases of snake envenomation by M. l. obtusa in Northwestern Iran, which occurred in spring 2019 and resulted in severe clinical courses and long-term musculoskeletal disabilities in some of the bite survivors. In three cases, a fasciotomy had to be performed, affecting the arm of a 15-year-old boy, the hand of a 36-year-old man, and the leg of another, 30-year-old man. In the latter case, extensive necrosis led to the amputation of the leg at the knee. All five patients received polyvalent anti-snake venom from the Razi Vaccine and Serum Research Institute, Karaj, Iran [56]. Cattaneo (2020) provides the first literature record of a bite incident by M. l. schweizeri. The victim, a young woman bitten on the right hand, was transferred to the hospital, where a sodium bicarbonate therapy was applied, coupled with the admission of drugs helping to replenish electrolytes and body fluids. The bitten limb swelled to the armpit, accompanied by pain, increased blood sugar and platelets, a reduction in red blood cells, minor hypotension and a decreased heart rate. The patient was discharged after 2 days, although the swelling and pain in the affected limb needed some additional days to dissolve [57]. Finally, Abukamar et al. (2022) reported of an envenomation by M. l. obtusa in Jordan. A 36-year-old male farmer bitten on his left foot presented to his local hospital, with initial symptoms such as dizziness and burning pain in the left leg. His bitten foot and ankle were swollen and hot, with extensive ecchymosis at the bite site. Despite treatment with antivenom, intravenous fluids and antibodies, his condition worsened. Even after transfer to a tertiary hospital in Amman, his platelet count continued to drop. Although neutrophilic leukocytosis and normochromic normocytic anemia were diagnosed, the patient finally recovered, and was discharged after 5 weeks [58].

Recommendations for snake envenomation prevention

Since the risk of snake envenomation is a primary concern in Cyprus, educational workshops for occupational outdoor groups such as mosquito control workers, hunters, shepherds, farmers, forestry employees and game wardens are critical for raising awareness of the risks and prevention of snake envenomation. Workshops should also be offered to rural communities and schools and include the promotion of non-lethal methods for preventing human-viper conflict such as snake deterrence or translocation. The risk of encounters between people and M. l. lebetina in Cyprus can be further reduced by legally protecting valuable snake habitats such as wild riparian areas and rocky slopes with confirmed M. l. lebetina populations, with prohibition of land transformation and strict regulations concerning further anthropogenic interventions (e.g., grazing). This could be achieved by designating new areas for the Natura 2000 network of the European Union. In all conservation areas, hunting should be prohibited.

Finally, a major contribution towards reducing the risk of snake envenomation in agricultural landscapes and gardens is the removal of organic waste and other structures attracting rats, and of wooden debris and other elements serving as potential snake shelters (H.-J. Wiedl, pers. comm., 29 March 2014).

Limitations of the study and suggestions for research protocol improvement

While the collection of data on annual hospital admissions due to snake envenomation in the Republic of Cyprus is a novel step towards a better understanding of the island’s snakebite epidemiology, the research protocol for further studies should include additional information, which will allow for a more precise snakebite data analysis. Since all records of hospital-admitted patients were based on the ICD-10 code T63.0, other ICD-10 codes related to snake envenomation (i.e., X20, contact with venomous snakes and lizards) were generally not listed by the hospitals, with exception of the two fatal cases, where the underlying causes of death were coded X20. However, X20 would be highly suitable for the non-fatal cases as well, as it explicitly includes vipers. Additionally, the applied ICD-10 code T63.0 can be split into four subcategories: accidental (001), intentional self-harm (002), assault (003) and undetermined (004) [59]. Although this sub-division was not provided for the dataset of this study, it can be assumed that all of the registered envenomations on Cyprus occurred accidentally (T63.001), as no case of assault or intentional self-harm (i.e., attempted suicide) involving snakes has – to the best of our knowledge – ever been published for Cyprus. Although this article provides for the first time systematically collected data on snakebite epidemiology in the Republic of Cyprus, it is doubtful that all cases of snake envenomation between 2013 and 2019 were included. This point can be illustrated by one incident in which an author of this article (DJ) was bitten on the back of his hand while handling a large male M. l. lebetina in Polis (Paphos district) on 29 May 2014. Although the bite was delivered into a safety glove, one fang penetrated the glove and punctured the skin. The bitten herpetologist was subsequently transferred to Polis Rural Hospital where he was given injections of cortisone (Solu-Cortef) and antihistamines (Phenergan). As no signs of envenomation could be detected, he was discharged after treatment. This bite accident, consequently, is not included in the 2014 record of ICD-10-coded diagnosis for Polis Rural Hospital. In fact, no case of snake envenomation was recorded in Polis Hospital during that year. Hence, future surveys on snakebite-related hospital admissions in Cyprus should also include incidents which might be considered as minor due to the absence of envenomation signs. Our dataset also does not show whether the 288 snakebite admissions refer to 288 or less persons. Accordingly, we cannot exclude the possibility that a person was bitten and admitted repeatedly to public hospitals, although the likelihood of such an occurrence can be considered as rather low. Yet, knowing the exact number of snakebite patients is critical for the calculation of incidence rates. As the recorded data do not include information on the distribution of age group and sex over month of admission and length of stay, it is not possible to investigate differences between seasonal peaks of snake envenomation in males and females in Cyprus, nor between the affected age groups over the year. It is further not possible to examine the data for a correlation between age group (and sex) and length of stay in hospital. In the same way, the missing information of the monthly distribution of length of stay prevents an analysis of possible seasonal trends in this regard. Protocols of future retrospective reviews could help to fill this gap by including this information. Additionally, the missing information on the localities where the bite accidents occurred currently prevents a statistic of snake envenomation in each district. As snakebites often take place in remote areas, people may travel large distances and cross borders to reach the nearest hospitals. Hence, to conclude from the frequency of snakebite-related admissions in a certain hospital to the presence of nearby areas with a possibly increased risk of snake envenomation, or with higher abundance of M. l. lebetina, is fraught with uncertainty. Therefore, recording the location of the accidents will help to identify snake envenomation hotspots and enable a snakebite statistic for each district. Furthermore, the snake species responsible for each bite should be recorded, if reliable identification is possible, in order to distinguish between bites by front-fanged and non-front-fanged snakes in Cyprus. This is necessary to determine whether a potential life-threatening envenomation (M. lebetina), a mild envenomation at most (M. insignitus, T. fallax), or no envenomation (any other snake species) has occurred. A correct snake species identification is also very helpful for a better assignment of clinical courses to the corresponding species. In the same way, the documentation of the major envenomation symptoms will facilitate distinguishing between potentially life-threatening and mild clinical courses, which is not currently possible with the data at hand. These points should be addressed by creating a more comprehensive, systematic reporting system for snake envenomation on Cyprus, which should include data of admissions from public as well as private hospitals. Finally, the establishment of a poison information center in Cyprus would be highly useful for a more comprehensive collection of data related to snake envenomation on the island.