Travaux du Muséum National d’Histoire Naturelle «Grigore Antipa» Vol. 58 (1–2) pp. 7–16 DOI: 10.1515/travmu-2016-0005 Research paper

Terrestrial Arthropods as a Public Health Issue in South–Eastern Cristina PREDA1, Ruben IOSIF1, *, Rodica TUDORAN2, Liliana Ana TUȚĂ2

1Faculty of Natural and Agricultural Sciences, Ovidius University of Constanța, 1 Aleea Universității, Building B, 900470 Constanța, Romania 2Faculty of Medicine, Ovidius University of Constanța, 1 Aleea Universității, Building B, 900470 Constanța, Romania *corresponding author, e–mail: [email protected]

Received: November 8, 2015; Accepted: February 22, 2016; Available online: April 20, 2016; Printed: April 25, 2016

Abstract. Little is known about the prevalence and severity of allergic reactions caused by terrestrial arthropods in Romania although bites and stings of arthropods represent a widely recognized public health issue. We conducted a retrospective study in Constanța, the largest city at the Romanian coast, and documented 207 cases during 2013–2014, representing 0.5% of the total number of records at the Emergency Department of the County Clinical Emergency Hospital. Young men and women presented themselves more often to the hospital to report this type of injuries and most arthropods causing allergic reactions were not identified. Our study brings novel information on the prevalence of injuries inflicted by terrestrial arthropods on the human adult population at the Romanian Black Sea coast, it highlights existing knowledge gaps and provides information on which to base future guidelines.

Key words: human health, insect, spider, centipede, Romania, prevalence, sting, bite, venom.

introduction Terrestrial arthropods have the potential to induce clinical manifestations of various degrees of severity in humans, ranging from minor irritation to anaphylaxis, a life–threatening allergic reaction (Golden, 2007). Four classes of arthropods are of general interest from this point of view: Chilopoda, including centipedes; Diplopoda, including millipedes; Arachnida, including scorpions (Scorpiones), spiders (Araneae), ticks and mites (Acari); and Insecta including bugs (Hemiptera), thrips (Thysanoptera), cockroaches (Blattodea), locusts (Orthoptera), lice (Phthiraptera), caterpillars (Lepidoptera), flies and mosquitos (Diptera), beetles (Coleoptera), bees, wasps, hornets and ants (Hymenoptera), fleas (Siphonaptera) (Burns, 2010). Toxin enzymes of the arthropods in the tropics were documented to affect all renal structures of the human victims, finally triggering tubular necrosis (Sitprija, 2008). In Central Europe, local and systemic reactions in humans are most frequently caused both by blood–sucking insects (mosquitoes and flies) and by venomous insect stings (honeybees and certain social wasps) (Przybilla & Ruëff, 2012). According to recent studies, insects represent one of the three most common triggers for anaphylaxis (Tracy, 2011). In Germany, at least 75% of the population is susceptible to local allergic reactions caused by haematophagous insects while large local allergic reactions caused by insect venom occur in up to 25% of the population. About 20 documented deaths occur in Germany per year following insect venom induced anaphylaxis (Przybilla & Ruëff, 2012). Thus, hymenopterans in the Aculeata group which includes true wasps, bees and ants, are considered of particular interest in terms of allergic 8 Cristina PREDA, Ruben IOSIF, Rodica TUDORAN, Liliana Ana TUȚĂ sting reactions (Bilo et al., 2005). Such reactions are of concern to the researchers, healthcare practitioners as well as the general population because they contribute to the deterioration of quality–of–life, also through emotional distress (Oude Elberink et al., 2002). Therefore, bites and stings from arthropods, reptiles and marine organisms are widely recognized as a major public health problem (Konings et al., 2007; WHO 2001). Proper education in terms of risk factors and effective management of clinical reactions caused by arthropods is of critical importance in order to reduce the negative effects on public health as well as healthcare costs. More than 3000 persons with tick bites, adults and children, were recorded at the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” in Bucharest between January 2013 and July 2014 (www.mateibals.ro). In recent years, researchers attempt raising public awareness on arthropod bites and recommend guidelines for bite avoidance (Goodyer et al., 2010). In accordance, the Ministry of Health of Romania as well as other national research institutions (e.g. aforementioned institute) provide recommendations for the general population regarding what to do in case of stings and bites of insects, spiders, and ticks and how to prevent such injuries (www.ms.ro). Nevertheless, little is known about the prevalence, epidemiology and severity of clinical reactions caused by terrestrial arthropods in Romania. The aim of this study was to investigate the prevalence of allergic reactions caused by terrestrial arthropods at the Romanian Black Sea coast, and to raise awareness on this public health issue. Terrestrial arthropods are also important agents for several diseases (e.g. malaria, borreliosis), however this aspect was beyond the scope of the current study. material and methods A retrospective study concerning the prevalence of allergic reactions in adult patients triggered by stings or bites of terrestrial arthropods was conducted in the most important Emergency hospital in south–eastern Romania: “Sf. Apostol Andrei” Clinical Emergency Hospital of Constanța. Constanța has a population of ~300 thousands being the largest city at the Romanian Black Sea coast but the hospital serves the entire population of south–eastern Romania (www.spitalulconstanta.ro). We screened the registries of the Emergency Department (ED) for records of admissions due to stings and bites of terrestrial arthropods in the last two years, namely 2013 and 2014, starting from late April (20th) until October (1st) since this is a period of intense activity for most terrestrial arthropods and therefore most likely to yield the information we sought. We extracted from the registries data concerning the age, gender, residence, date of hospital admission and outcome of the individuals stung or bitten as well as the arthropod considered responsible for inflicting the injury. Regarding residence, all records were classified in two major categories: i) residents of Constanța County and ii) residents of other counties. Within residents of Constanța County category, we further divided the records in two more groups, namely urban areas (for residents of Băneasa, Constanța, Eforie, , , Năvodari, Negru Vodă, and ) and rural areas, all of the remaining records. For the purpose of this study, following the general suggestions of Bilo et al. (2005) and Clark et al. (2005), we divided the outcome of the stings/bites in two categories: local and systemic reactions. We considered local reactions as skin rash, hives, or swelling, while systemic reactions included components of the skin, gastrointestinal, respiratory, renal and/or cardiovascular systems. The involvement of two or more organ systems or hypotension alone was used to describe anaphylaxis. Terrestrial Arthropods as a Public Health Issue in South–Eastern Romania 9

Categorical variables were analysed using the chi–square test (χ2) or Fisher– Freeman–Halton test, as appropriate. The Fisher–Freeman–Halton test is the Fisher’s exact test generalized by Freeman and Halton to greater than 2 × 2 crosstabulation tables (Conover, 1980). We used “MASS” package (Venables & Ripley, 2002) in R version 3.1.2 (R Core Team, 2013) and Systat 13 (www.systat.com) to determine the levels of statistical significance. The significance level, α, was set at 0.05 in all statistical analyses.

results We documented 207 cases of persons accusing allergic reactions to stings or bites of terrestrial arthropods in the period under investigation, representing 0.5% of the total number of cases recorded at the ED. The overall number of persons stung/ bitten was higher for males than females (56% vs 44%) but no significant differences were observed between genders (χ2= 3.01, df = 1, p=0.08). We detected an association between the responsible arthropod and gender of the stung/bitten person (p=0.001). Differences were also detected in terms of age (χ2= 94.79, df = 7, p <0.001). While the average age of the patients was 42±17, age range from 16 to 93 years, more young males (20–29–year and 30–39–year age groups) and females (20–29–year age group) arrived at the ED (p = 0.01; fig. 1). Roughly one fifth of the persons stung/bitten by arthropods are not residing in Constanța County, 16% are residents of rural areas of Constanța County while the rest live in urban areas of the same county. Differences were observed in terms of the time of year that people reported stings and bites, most of the people–arthropod “encounters” being recorded in late summer for both years collectively (χ2 = 84.67,

Fig. 1 – Age–sex distribution of persons recorded with stings/bites of arthropods (n=91 for females and 116 for males which consulted at the hospital). 10 Cristina PREDA, Ruben IOSIF, Rodica TUDORAN, Liliana Ana TUȚĂ df = 7, p < 0.001). June was the month with the highest number of records in 2013 and July in 2014 (Fig. 2). Insects are the main group of arthropods considered responsible for the majority of stings recorded throughout the studied period (~91%). However, the type of arthropod inflicting the sting or bite was unidentified in roughly 70% of the records and listed as “sting of an insect” in the registry (Insecta varia in fig.3). Hymenopterans, either bees or wasps, were recorded in ~20% of the cases and mosquitos (Diptera, Nematocera) in ~1%. Few other arthropod inflicted injuries, like bites of centipedes (Chilopoda, 2%) or spiders (Arachnida–Araneae, 5%) and ticks (Arachnida–Acari, 2%) were recorded as well in the months under study. An association between the “culprit” arthropod and the time of year when the sting/bite took place was observed (p=0.04; Fig. 3). Most patients (~91%) received treatments with corticosteroids and antihistaminic drugs and were discharged in good health the same day as the admission. Roughly 93% suffered local reactions while systemic reactions were recorded in 7% of the cases. Only 1% needed to be hospitalized, roughly 7% were referred to the local hospital for infectious diseases and four persons (~2%) left the ED. No fatal injuries or disabilities were recorded to our knowledge.

discussions We investigated the prevalence of allergic reactions caused by terrestrial arthropods in the largest city at the Romanian Black Sea coast. Roughly one person arrived each day at the ED of the hospital in Constanța accusing being stung or bitten by a terrestrial arthropod in the period under investigation. Depending on the climate, estimates of persons stung at least once by Hymenoptera range between 56.6 and 94.5% of the general adult population (Antonicelli, Bilo, & Bonifazi, 2002). Therefore, arthropod–human interactions might be more frequent than previously realized

Fig. 2 – Monthly distribution of persons, which consulted at the hospital, stung/bitten by arthropods (n=122 in 2013; n=85 in 2014). Terrestrial Arthropods as a Public Health Issue in South–Eastern Romania 11

Fig. 3 – Main groups of arthropods considered responsible for stinging/biting humans recorded per month (n=207). The categories in the graph refer to (in order, from top to bottom): ticks, spiders, centipedes, bees and wasps, mosquitos. “Insecta varia” refers to unidentified stings or bites of arthropods, generally considered as “stings of insects”. and their number is likely to increase in the near future due to shifts in organisms’ distribution and abundance and new species arrivals and establishment in regions previously unoccupied (i.e. alien species) (Hulme & Philip, 2009; Hulme, 2014). For example, in Spain, a 27 year old woman suffered an episode of severe anaphylaxis after being stung by ants while she was handling wood from South America. The woman had no record of adverse reactions to stings by other hymenopteran species. The ants were subsequently identified as Solenopsis invicta Buren, 1972, the red imported fire ant (Fernandez–Melendez et al., 2007). S. invicta is native to South America and was nominated for the 100 World’s Worst Invaders list compiled by the Invasive Species Specialist Group (ISSG, 2014). Furthermore, the popularity of exotic pet trade is another cause of concern related to species welfare and conservation as well as public health and safety throughout the European Union (Engler & Parry-Jones, 2007; Tolend et al. 2012). In our study, one 19–year old female reported an allergic reaction to a tarantula bite. In our opinion, rather than being a case of misidentification, the injury was accidentally caused by the handling of a tarantula pet. Therefore, we emphasize and completely agree with the recommendations of the World Health Organisation regarding the complexity of medical problems raised by imported non–native species and the necessity of clinicians and information officers at poisons centres to be informed about the diagnosis and management of stings/bites of both native and non–native animals (WHO 2001). Although males outnumbered females in our study, our results suggest that men and women are equally likely to be stung or bitten by terrestrial arthropods. Some studies found that men are more frequently and more severely affected by hymenoptera induced allergic reactions but no consensus has been reached on the subject so far (Bilo & Bonifazi, 2009; Chen et al., 2008). Not surprisingly, more young males and 12 Cristina PREDA, Ruben IOSIF, Rodica TUDORAN, Liliana Ana TUȚĂ females which consulted at the hospital reported such stings and bites. This can be explained by the fact that people in these age classes are more active and possibly spending more time performing various activities outdoors therefore increasing their chances of interacting with arthropods (e.g. farming, beekeeping, jogging). Another suggestion is that they are more prone to consult a physician once such an event occurs compared to older people (e.g. differences in education). The most frequently documented sites on the body where the arthropods inflicted injuries were the face and limbs. Although one could observe overall a decrease in the number of reports with increasing age, it is interesting that a large proportion of females over 60 years of age were stung or bitten. One possible explanation is that women in this age group also spend a considerable amount of time outdoors, e.g. gardening or caring for their grandchildren. Differences in daily activities might also explain the interesting association between the gender of the person stung/bitten and the type of arthropod responsible. Nevertheless, further investigations in this regard are necessary. Most of the people recorded in our study are residents of urban environments, either the city of Constanța or other urban areas in Constanța County. Approximately 20% of the records are of people residing in other and particularly in Bucharest. Irrespective of their residence, we assume that the stinging or biting took place somewhere in Constanța area since they presented themselves at the ED of the local hospital. We believe this is due to the fact that Constanța is a popular touristic destination, especially during the warm season when our investigation took place. We suggest designing a short questionnaire to be filled in by the patients that would include the geographic location and circumstances of the actual sting or bite as well as the mechanical cause of the reaction (e.g. simple introduction of bristle, dart or mouth pieces, venom injection). This questionnaire would be informative in identifying the areas of concern and reducing the risk of exposure to such hazards. A study performed in UK found that 15% of the 47 recorded cases of fatal anaphylaxis due to insect stings occurred at work, 32% in the garden, and 34% at home while 5% occurred in bed (Pumphrey, 2004). Terrestrial arthropods are represented mainly by insects, which are generally active in the warm months of the year. Accordingly, the highest number of admissions in the ED per month for both years was recorded in July and August. June is the month with the most obvious difference in number of records between the two years under investigation, which could be related to climatic conditions. For example, one can observe the increased amount of precipitation (122.6 mm vs. 64 mm) and number of days raining (15 vs. 5) in 2014 compared with 2013 in Constanța area (data according to TuTiempo.net), which would restrict the period of activity for insects as well as time spent outdoors by people. The severity of the clinical reaction is clearly influenced by a combination of factors related to the responsible arthropod, the host and the environment in which the injury was inflicted. Approximately 70% of the records in our study are referred to as “sting of an insect” while roughly 20% of the stings are attributed to hymenopterans, either wasps or bees. This might be because stings of hymenopterans are occurring most frequently but it might also be because wasps and bees are generally more familiar to us than other arthropods, thus one might more easily observe and recognize a hymenopteran. Baker et al. (2014) performed a picture–based survey aimed at determining the accuracy of adults in identifying honeybees, wasps, bald– face hornets, and yellow jackets and 2 insect nests. They found that the honeybee was the most accurately identified insect by 91.3% of the 640 participants to the study Terrestrial Arthropods as a Public Health Issue in South–Eastern Romania 13 and only 3.1% of the participants correctly identified all 6 stinging insects and nests. Also, men and those participants who were stung by at least 4 insects were more successful in insect identification. We could not identify any arthropod at species level based on the data available for our study. However, several species are likely candidates for venom–induced allergic reactions in this region such as the honeybees (Apis mellifera Linnaeus, 1758), wasps (Vespula germanica (Fabricius, 1793), Vespula vulgaris (Linnaeus, 1758), Polistes sp.), hornets (Vespa crabro Linnaeus, 1758) or bumblebees (Bombus sp.). Clinical history, measurement of specific IgE antibodies in the serum and skin–prick test are successfully used to diagnose insect–sting allergy (Järvinen & Celestin, 2014). Allergens in Hymenoptera venom are species–specific but cross–reactions are frequently encountered (Przybilla & Ruëff, 2012). For example, cross–reactivity with Vespula venom is considered responsible for most of the anaphylactic reactions after Vespa crabro stings in Central Europe (Hemmer, 2014). The identification of the initiating factor and long–term treatment are recommended in the case of patients that have suffered an anaphylactic reaction in order to prevent further episodes. Bites of centipedes, spiders, ticks and mosquitos were also identified as causes of clinical manifestations in our study, albeit mostly local reactions. Centipedes are notorious for inflicting painful bites to humans but insights into the composition, evolution, mechanisms of action of their venoms have only recently been revealed (Undheim et al., 2015). Though rarely fatal, centipede envenomation poses a significant risk particularly to people sensitized to hymenopteran venom allergens (Undheim & King, 2011). Iovcheva et al. (2008) reported an increase in the number of centipede envenomation records in recent years in Varna region of Bulgaria, possibly caused by Scolopendra cingulata Latreille, 1829, a common species in Europe. Among spiders, the genra Latrodectus, including the European black widow L. tredecimguttatus (Rossi, 1790), and Loxosceles, including the Mediterranean recluse spider L. rufescens (Dufour, 1820), are usually considered of medical importance (Alexakis et al., 2015). Five other species in five different genera causing relatively mild symptoms to people were identified in a study performed in urban areas in Switzerland. The authors estimate the number of species in Europe capable to perforate human skin and affect human health to be considerably larger, roughly 100–200 species (Nentwig, Gnadinger, Fuchs, & Ceschi, 2013). Allergens in mosquitoes’ saliva may cause severe reactions in humans, which are likely under–diagnosed and under–treated (Peng & Simons, 2007). Several other arthropods like caterpillars (Vega et al., 2011; 2014) (e.g. Thaumetopoea processionea (Linnaeus, 1758), Hyphantria cunea (Drury, 1773)), cockroaches (e.g. Blattella germanica (Linnaeus, 1767)), bedbugs (e.g. Cimex lectularius Linnaeus, 1758), flies (e.g. Tabanus sp.), beetles (e.g. Paederus sp., Harmonia axyridis Pallas, 1773), scorpions (Euscorpius carpathicus (Linnaeus, 1767)), can pose a threat to human health in Romania and are rarely suspected by patients or physicians. Adult bedbugs, C. lectularius, can easily be transported with luggage and can survive even one year without feeding while adult fleas can survive starvation for a few months (Burns, 2010; Cobb, 1994). While we do encourage people to be keen observers of nature and, if easily and safely possible, to capture the arthropod inflicting an injury for identification, we would also suggest a closer collaboration between arthropod specialists (e.g. entomologists) and healthcare professionals to develop standardized operating procedures and methods to increase the accuracy of predicting the group of arthropods responsible for various stings or bites, the occurrence and severity of the allergic reactions. In our opinion, 14 Cristina PREDA, Ruben IOSIF, Rodica TUDORAN, Liliana Ana TUȚĂ developing arthropod–group specific protocols of management of allergic reactions would prove beneficial in terms of patients’ welfare as well as healthcare cost. Rafeeq and Dhariwals (2013) also suggest the development of an electronic record template for quick identification of symptoms and corresponding recommended management in order to improve the management of insect–sting allergic reactions in a community hospital emergency department in the United States. Our study brings novel information on the prevalence of injuries inflicted by terrestrial arthropods on the human adult population at the Romanian Black Sea coast, it provides data on which to base future guidelines and highlights existing knowledge gaps (e.g. identifying the areas of highest concern or percentage of anaphylaxis fatalities caused by terrestrial arthropods). The results of our study should be interpreted with caution as they correspond to a subset of the population that decided to consult at the hospital. We are aware that similar studies should be conducted at larger spatial and time scales for better estimates therefore we encourage performing a national survey using various methods that encompass the complexity and provide greater insight on the phenomenon. Combining data from prospective studies with data recorded in hospital registries would allow for a more reliable estimate of the magnitude of the phenomenon in Romania and thus ensure proper information and education of the general population, practitioners and decision makers.

acknowledgements This work received financial support through the project entitled “CERO – Career profile: Romanian Researcher”, grant number POSDRU/159/1.5/S/135760, cofinanced by the European Social Fund for Sectorial Operational Programme Human Resources Development 2007–2013. The authors gratefully acknowledge the suggestions received from Raluca Băncilă, Laurențiu Rozylowicz and the anonymous reviewers.

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