Bothrops Erythromelas

Clinical Case Reports and Reviews

Case Study ISSN: 2059-0393

Clinical, laboratorial, and epidemiological evaluation of patients bitten by Bothrops erythromelas in campina grande, Paraíba, Brazil, from June to December, 2009 Karla Patrícia de Oliveira Luna* Departamento de Biologia, Universidade Estadual da Paraíba – UEPB – Campina Grande, Brazil

Abstract Background: Blood tests like clotting time and bleeding time are tools that help physicians to predict snake envenomings and their management. Methods: In this study patients bitten by Bothrops eryhtromelas in Campina Grande, Paraíba, Brazil were analyzed front of blood alterations. Clinical and epidemiological data of those individuals to design which cities show the majority of the accidents were also made. Results: Pain was the most referred local manifestation by the individuals bitten by the snake B. erythromelas followed by edema. Four patients presented haemorrhage after envenoming returning to normal after treatment. The predominance among male aging between 20 to 30 years old shows that this age range is the most affected by snake bites. In this study was observed the prevalence of the agriculture activity and the rural area. Haemorrhage was the most systemic manisfestation observed in this study. Conclusion: In the present study we verified the importance of evaluating hematological parameters on snake envenomings in accordance with clinical and epidemiological data.

Introduction Immunological evaluation after snake bites is not largely studied, as well as, not well known on individuals bitten by snakes. In this work we Snake envenomings are a health problem mainly in rural areas analyzed the involvement of IL-10, IFN-γ and NO for patients bitten by of tropical and subtropical countries. In Brazil occur almost 30.000 the snake Bothrops erythromelas in Norteastern Brazil. snake bites annually, resulting in more than 100 deaths (0.4%) [1]. In northeastern Brazil Bothrops erythromelas is the edemic species Methods being responsible for 210 bites in Paraíba. People bitten by Bothrops erythromelas show local effects at the site of the bite like oedema, Patients ecchymosis, blisters and necrosis; systemic manifestations like gengival The project that originated this paper was approved by the ethics bleeding, hematuria and epistaxis, as well as blood disturbances [2]. committee of the hospital and all patients included in the study consent As B. erythromelas venom does not present miotoxic activiy [3] people to participate. Third five patients admitted to the hospital in Campina bitten by this snake don’t present large necrosis at the site of the bite. Grande with clinical diagnosis of Bothrops envenoming were included As most of envenomed individuals do not see the snake at the in this study. After a clinical evaluation, patients were classified as mild, moment of the bite and also do not bring the species to the hospital, moderate or severe envenomed. The mild group was characterized by diagnosis is based on clinical features [4]. Those clinical features also a local swelling, local bleeding and mild hemorrage; the moderate help physicians to classify envenomation as mild, moderate or severe, goup was characterized by more severe swelling, local bleeding and hemorrage; the sever group was classified as presented severe swelling, which will drive the treatment [5]. Local swelling at the site, bleeding local bleeding and blisters, and severe hemorrage. In each group and shock are used as prognostic, although those features have not individuals received specific antivenom. The mild group received 4 been tested rigorously [4]. vials of antivenom, the mild group recieved 8 vials and the severe group Only two works immunologically evaluated individuals bitten by snakes. Barraviera et al. [6] analyzed 31 patients bitten by the snakes Crotalus durissus terrificus and Bothrops jararaca. In that work it was observed an increase of IL-6 and IL-8 in all patients on the first days Correspondence to: Karla Patrícia de Oliveira Luna, Depto. de Biologia after envenomation. Laboratorial data showed leukocitosis, leucopenia Universidade Estadual da Paraíba-UEPB Rua Baraúnas, 351 - Bairro and neutrofilia. Ávila-Agueroet al. [7] analyzed children bittem by the Universitário - Campina Grande-PB, CEP 58429-500, Tel/Fax: 83 3315.3300; snake Bothrops asper in Costa Rica and observed a marked raise on IL-6 E-mail: [email protected] and IL-8 on admission time, returning after 72 hours treatment. TNF-α Keywords: epidemiology, snake envenomation, clinics showed a peak on 12 hours after admission. RANTES was increased in Received: September 21, 2015; Accepted: October 21, 2015; Published: October five patients. 24, 2015

Clin Case Rep Rev, 2015 doi: 10.15761/CCRR.1000177 Volume 1(10): 239-243 Oliveira Luna KP (2015) Clinical, laboratorial, and epidemiological evaluation of patients bitten by Bothrops erythromelas in campina grande, Paraíba, Brazil, from June to December, 2009

received 12 vials of antivenom (as prescribed by the Ministério da Results Saúde, 2001) [1]. The antivenom therapy was started as soon as possible to all individuals. Patients were studied as far as 48 hours after entrance Twenty seven patients had a confirmatory diagnosis of Bothrops at the hospital. In order to understand epidemiological features of envenoming based on the clinical observation and laboratorial tests. Bothrops envenomation in PB, information of patients included: Sixteen patients were classified as mild envenomation, seven patients name, local of event, time, area (urban or rural), age, sex, as well as site were classified as moderate envenomation and three were classified as of bite, type of snake, time between bite and entrance at the hospital, severe envenomation. haemorrage, swelling, clotting time, platelets number, complete blood Platelets count, bleeding time, local necrosis and systemic bleeding. Platelet count was as their lowest in only three patients as follows: Blood samples two mild and one severe envenomation. This data do not corroborate Individual blood samples (20 ml) were collected by venipuncture other studies [10] which claims that thrombocytopenia is a marked on admission, 24 hours and 48 hours after envenomation. Blood statistically significant process developed on envenomations by coagulation time was assessed using two tubes incubated 30 minutes Bothrops species. total at 37°C. Platelets were counted electronically in a automatized Clotting time and bleeding time system (Counter 19 – Wiener Lab). It is important to clarify that CDC and number of platelets were performed only under medical Clotting time was altered in 22 patients raising 12 hours after prescription. treatment, except for two of them which were yet incoagulable after treatment (Figure 1). Bleeding time was not altered in any patients. Statistical analysis Epidemiological evaluation Epidemiological evaluations is a transversal study using indirect documentation on snake envenomations attended in Campina Grande Table 1 shows the characterization of snake envenomations from June to December, 2010. All include patients presented medical attended and notified at the CEATOX-PB, following social and diagnosis for Bothrops envenomation. Data were collected from the demographic variables. When age of patients was evaluated, it was notification sheets of the Poison Information Center of Campina a greater frequency for 20-30 years old group (25%). When age was Grande. evaluated it was observed that male was the gender the most affected (89.28%). Total whole blood cell counting

Total whole blood cell counting (TWBCC) was not possible to 25 analyze statistically once not all patients had this parameter prescribed 20 s by the physician. As TWBCC is not predictable for envenomation, t n e i t physicians prescribe it only in severe cases were patient’s life is at risk. a 15 p

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However, this is an important parameter to evaluate, for example, to r e know the type of leucocytes involved in this envenomation before and b 10 m u after treatment. N 5

Epidemiological evaluation 0 Epidemiological analysis was carried out in order to evaluate 1 2 Coagulability important parameters as local of occurrence of the accident, like rural or urban areas, city of occurrence, sex, age, local of the bite, number of Figure 1. Coagulability of patients bitten by Bothrops erythromelas snake venom. vials used for treatment and time between bite and hospital admission.

The city of Campina Grande is located on Paraíba State, composed Table 1. Distribution of Bothrops erythromelas snake bites by sex. by 379.871 people, 46.8% men and 53.2% women [8]. The city is a converge pole, with around 232 neighbors cities, which drive to Age Campina Grande searching for services offered, including health 0-10 0-0% services [9]. 11-19 3-10.71% This study took place with help of the Poison Information Centre 20-30 7-25% (CEATOX-Campina Grande), a service offered by the Pharmacy 31-40 1-3.57% Department of the State University of Paraíba (UEPB) with the partnership of the Regional Hospital of Campina Grande. 41-50 5-17.85% 51-60 6-25% Clinical evaluation 61-70 3-10.71% Clinical evaluation of all patients was performed by the medical 71-80 0-0% staff of the hospital. 81-90 1-3.57%

Ethics 90-100 0-0%

This study was approved by the Ethics Committee of the Centro de n.i. 1-3.57% Pesquisas Aggeu Magalhães/FIOCRUZ, Recife. Total 27 – 100%

The majority of envenomations occurred in the rural area (89.25%) Table 3. Anatomical site of bite. rather than in urban area (10.71%). Local Bites occurred from June to December even though irregularly Pain 22 (Figure 2) and the city with most notifications was Taperoá (3 cases) Edema 16 (data not shown). Echimosis 3 Necrosis 0 The anatomical region of the bite most affected was feet (46.42%) Parestesia 9 followed by finger feet (17.85%) and hand finger (10.71%) (Table 3). Hiperemia 1 Accidents classified as mild envenomation were the most observed (50%) as we can observe by the number of antivenom vials used of platelet counts before treatment. This result is in agreement with (Figure 3). previous studies [11,12]. As low levels of platelet counts is related to the Most patients reached the hospital care into the 3 first hours after severity of envenomation we can suggest that the patients included in envenomation (46,42%) (Figure 3). this study presented most mild envenomation as their platelet counts were normal. Clinical evaluation Sano-martins et al. [13] observed that patients bitten by smaller Pain was the most referred local manifestation, in 22 patients, B. jararaca presented a higher platelet counts which could not be followed by edema. Systemic disorders were observed like hemorrhage completely understood, as incoagulability is more commonly observed [4] and head ache [7]. in individuals bitten by smaller than larger B. jararaca. Discussion Simple coagulation tests can be used to diagnose systemic envenoming and control the antivenom doses [14]. This study we Blood platelets play an important role in hemostasis, starting the observed 81.4% of patients presenting prolonged clotting time (data not development of hemostatic plugs [11]. In this study it was observed shown), which corroborate with other studies [10,15,16], as it is known that of the twenty-seven patients evaluated only 3 presented low levels that Bothrops venoms has the ability of activate blood coagulation [14]. Envenomation inflicted by snakes of the Viperidae family is usually 12 characterized by prominent local effects such as necrosis, haemorrhage, edema and pain [17,18]. Those effects, however, are not well neutralized 10 s t by the antivenom used [11,19], even though, they are the only effective n e

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a treatment for snake bite envenomation [20]. p

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e In the present study we observed that pain was the most referred b

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u local manifestation by the individuals bitten by the snake B. erythromelas N 2 (Figure 1), followed by edema (Figure 2). These data corroborate with other studies, either experimental [19,21] or with humans [1,11,22]. 0 jun jul ago set out nov dez There is a high quantity of components on Bothrops venoms that Months compromise haemostasis. So that it is common a high frequency of Figure 2. Distribution of Bothrops erythromelas bites according to seasonality – from June bleeding caused by this type of envenomation. Those bleedings can be to December, 2009. distinguished as local and systemic [13]. In the majority of the cases bleeding is stopped after antivenom therapy, although some brain Table 2. Distribution of snake Bothrops erythromelas bites by area. bleeding has been related in some cases which can lead patient to death [23]. Area Rural 24 In the present study 4 patients presented haemorrhage after Urban 3 envenoming returning to normal after treatment. All 4 patients were classified as moderate or severe envenomation and the type of Total 27 haemorrhage was epistaxis and gingival haemorrhage. The predominance among male aging between 20 to 30 years old 14 shows that this age range is the most affected by snake bites. These 12 data may indicate the insertion of young men in the work more than s t

n 10

e women. The Brazilian Ministry of Health data (2003) [24] show that i t a

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in 52.3% of notifications the prevalence is for 15 to 49 years old, which f o

e 6 correspond to the work force. Male were the most exposable to this b m

u 4 injury with 70% of the bites (Table 1). N 2 In this study was observed the prevalence of the agriculture activity 0 and the rural area. In Northeast region of Brazil it is observed a greater 0 a 1 1 a 3 3 a 6 6 a 12 12 a 24 mais 24 n.i. activity in the planting and harvest periods (Table 2). So that it may Time (hours) have a correlation between the frequency of snake bites and the period Figure 3. Time distribution of patients bitten by Bothrops erythromelas – June to for planting and harvest [9]. Those inferences reinforce the fact that December, 2009.

snake bites as a work accident. Furthermore, these data confirm the References results obtained by Kastiriratne et al. [25] who related that all over the 1. Avila-Agüero ML, París MM, Hu S, Peterson PK, Gutiérrez JM, et al. (2001) Systemic world rural activity is a risk factor for snake bites. cytokine response in children bitten by snakes in Costa Rica. Pediatr Emerg Care 17: 425-429. [Crossref] Seasonality for snake bites must be taken as an important fact 2. Barraviera B (1995) Acute-phase reactions including cytokines in patients bitten by which can drive educational prevention. In Southern and South of Bothrops and Crotalus snakes in Brazil. Journal of Venomous Animals and Toxins 1: Brazil snake accidents usually occur from October to April which is 11-22. the most warm and rainy period of the year for those regions (Brazil, 3. Bucaretchi F, Herrera SR, Hyslop S, Baracat EC, Vieira RJ (2001) Snakebites by 2003) [24]. In Northeastern the accidents occur mostly between May Bothrops spp in children in Campinas, São Paulo, Brazil. Rev Inst Med Trop Sao and September with decay after October [9]. Paulo 43: 329-333. [Crossref] Victims were most affected in the inferior members as feet and 4. Cardoso JL, Fan HW, França FO, Jorge MT, Leite RP,et al. (1993) Randomized comparative trial of three antivenoms in the treatment of envenoming by lance-headed finger feet. [22] and [26] also related feet (43.1%) as the most affected vipers (Bothrops jararaca) in SÃ£o Paulo, Brazil. Q J Med 86: 315-325. [Crossref] region of the body. So that the use of protection equipments as gloves and boots are indicated (Table 3). 5. Chacur M, Picolo G, Gutierrez JM, Teixeir CFP, Cury Y (2001) Pharmacological modulation of hyperalgesia induced by Bothrops asper (terciopelo) snake venom. Mild envenomations were the most observed in this study. This is Toxicon 39: 1173-1181. [Crossref] in accordance with period between bite and hospital care and also with 6. Franca FOS, MÃ¡laque CMS (2003) Acidente BotrÃ³pico. In: Animais Peconhentos other authors [5,27]. Although [10] showed that time between bite and no Brasil: Biologia, Clinica e Terapeutica dos Acidentes. Haddad Jr, et al. (Eds.), cap. 6, p. 72-86, ed. Sarvier. hospital care is not related. 7. Gutierrez JM, Chaves F, Gené JA, Lomonte B, Camacho Z, et al. (1989) Myonecrosis The most clinical features observed in this study were pain and induced in mice by a basic myotoxin isolated from the venom of the snake Bothrops edema. It is well known that Bothrops evenomings are characterized nummifer (jumping viper) from Costa Rica. Toxicon 27: 735-45. [Crossref] by pain, edema, haemorrhage, local necrosis, ecchimosis, blisters [1,2] 8. Hutton RA, Warrell DA (1993) Action of snake venom components on the haemostatic (Table 4). system. Blood Rev 7: 176-189. [Crossref] Haemorrhage was the most systemic manifestation observed in this 9. Intituto Brasileiro de Geografia e EstatÃstica, 2007. study, as also related by other authors [10,28] followed by headaches. 10. Kamiguti AS, Matsunaga S, Spir M, Sano-Martins IS, Nahas L et al. (1986). Alterations This haemorrhage was soon stopped after antivenom therapy, except of the blood coagulation system after accidental human inoculation by Bothrops for one patient who presented epistaxis and remained bleeding for jararaca venom. Braz J Med Biol Res 19: 199-204. [Crossref] more 2 days after treatment (Table 5). 11. Kamiguti AS, Zuzel M, Theakston RD (1998) Snake venom metalloproteinases and disintegrins: interactions with cells. Braz J Med Biol Res 31: 853-862. [Crossref]

Conclusions 12. Kasturiratne A, Wickremasinghe AR, de Silva N, Gunawardena NK, Pathmeswaran A, et al. (2008) The global burden of snakebite: a literature analysis and modelling based In the present study we verified the importance of evaluating on regional estimates of envenoming and deaths. PLoS Med 5: e218. [Crossref] hematological parameters on snake envenomings in Northeastern 13. Kouyoumdjian JA, Polizelli C, Lobo SM, Guimares SM (1991). Fatal extradural Brazil, specially on Bothrops envenomation. These data will allow us to haematoma after snake bite (Bothrops moojeni). Trans R Soc Trop Med Hyg 85: 552. better understand the variations on the different envenomings as well [Crossref] as to design better approaches on new therapies. 14. Lemos JC, Almeida TD, Fook SML, Paiva AA, SimÃµes MOS (2009) Epidemiologia Also, epidemiological data can lead us to corroborate with a more dos acidentes ofÃdicos notificados pelo centro de assistÃªncia e informaÃ§Ã£o toxicolÃ³gica de campina grande (Ceatox-CG), ParaÃba. Revista Brasileira de accurate notification for this type of health problem. Epidemiologia 12: 50-59.

15. MinistÃ©rio da SaÃºde de Brasil (2011) Manual de diagnÃ³stico e tratamento de acidentes por animais peÃ§onhentos. FundaÃ§Ã£o Nacional de SaÃºde. Table 4. Local manifestations after Bothrops erythromelas snake bite. 16. Moreno E, Queiroz-Andrade M, Lira-da-Silva RM, Tavares-Neto J (2005) Clinical and Local epidemiological characteristics of snakebites in Rio Branco, Acre. Rev Soc Bras Med Pain 22 Trop 38: 15-21. [Crossref] Edema 16 17. Picolo G, Chacur M, Gutiérrez JM, Teixeira CF, Cury Y (2002) Evaluation of Echimosis 3 antivenoms in the neutralization of hyperalgesia and edema induced by Bothrops jararaca and Bothrops asper snake venoms. Braz J Med Biol Res 35: 1221-1228. Necrosis 0 [Crossref] Parestesia 9 18. Ribeiro LA, Jorge MT, Iversson LB (1995) Epidemiology of accidents due to bites of Hiperemia 1 poisonous snakes: a study of cases attended in 1988. Rev Saude Publica 29: 380-388. [Crossref]

19. Rosenfeld D (1971) Symptomatology, pathology, and treatment of snako bites in South Table 5. Systemic manifestations after Bothrops erythromelas snake bite. America. In: Bucherl W, Buckley EE (Eds.), Venomous animals and their venoms. New york. Academic Press, 79. v. 2, p. 345-384. Systemic 20. Sano-Martins IS, Fan HW, Castro SC, Tomy SC, Franca FO (1994) Reliability of the Hemorrhage 4 simple 20 minute whole blood clotting test (WBCT20) as an indicator of low plasma Thow up-diarrhea 3 fibrinogen concentration in patients envenomed by Bothrops snakes.Toxicon 32: 1045- Head ach 7 1050. [Crossref] Sleepy 1 21. Sano-Martins IS, Santoro ML, Morena P, Sousa-e-Silva MC, Tomy SC, et al. (1995) Turvation 1 Hematological changes induced by Bothrops jararaca venom in dogs. Braz J Med Biol sickness 1 Res 28:303-312. [Crossref] Total 17 22. Sano-Martins IS,Santoro ML (2003) Distubios hemostaticos em envenenamentos por

animais peconhentos no Brasil. In: Animais Peconhentos no Brasil. Biologia, Clinica e Haematological evaluation of patients bitten by the jararaca, Bothrops jararaca, in Terapeutica dos Acidentes. (1stedn), Sao Paulo: Sarvier; 289-309. Brazil. Toxicon 15: 1440-8. [Crossref]

23. Santoro ML1, Sousa-e-Silva MC, Gonçalves LR, Almeida-Santos SM, et al.(1999) 25. Teixeira Cde F, Fernandes CM, Zuliani JP, Zamuner SF (2005) Inflammatory effects of Comparison of the biological activities in venoms from three subspecies of the South snake venom metalloproteinases. Mem Inst Oswaldo Cruz 100: 1812-1814. [Crossref] America rattlesnake (Crotallus durissus terrificus, C. durissus cascavella and C. durissus collilineatus). Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 122: 26. Vasconcelos CM, Valença RC, Araújo EA, Modesto JC, Pontes MM, et al. (1998) 61-73. [Crossref] Distribution of 131I-labeled Bothrops erythromelas venom in mice. Braz J Med Biol Res 31: 439-443. [Crossref] 24. Santoro ML1, Sano-Martins IS, Fan HW, Cardoso JL, Theakston RD, et al. (2008) 27. Warrell DA (2010) Snake bite. Lancet 375: 77-88. [Crossref]

Copyright: ©2015 Oliveira Luna KP. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Clin Case Rep Rev, 2015 doi: 10.15761/CCRR.1000177 Volume 1(10): 239-243