version ISSN 0104-7930
J. Venom. Anim. Toxins vol. 3 n. 2 Botucatu 1997
INFECTIONS IN THE BITE SITE AFTER ENVENOMING BY SNAKES OF THE Bothrops GENUS
1 Department of Internal Medicine of the Center of Biomedical Sciences of the Federal University of Uberlândia, state of Minas Gerais, Brazil.
ABSTRACT. Envenomation caused by snakes of the Bothrops genus produces a lesion in the bite site and can result in extensive necrosis. The dead tissue can be secondarily infected by bacteria that come from the snake, and the bacteria can be inoculated at the moment of the bite. The bacteria that most commonly cause infection are the enterobacteria, mainly Morganella morganii, Proteus rettgeri, Enterobacter sp., and Escherichia coli. Group D streptococci including here Enterococcus sp. and the Bacteroides sp. are also involved. Based on a study of the sensibility of these bacteria, it has been suggested that this infection must be treated with chloramphenicol, as a sole antimicrobial agent, or with the combinations of benzylpenicillin or ampicillin with aminoglycoside or trimethoprim/sulfamethoxazole. Although Governmental Health Services do not recommend the prophylactic use of antimicrobial drugs, it is not yet clear that such a procedure would not be useful in cases with a high probability of infection.
KEY WORDS: snakebite, Bothrops, infection, antimicrobial agents, treatment.
GENERAL ASPECTS: Brazilian venomous snakes belong to the Viperidae and Elipidae families, and only Crotalinae (Bothrops, Lachesis and Crotalus genera) belong to the Viperidae family. Species of the Bothrops genus are distributed almost all over Brazil(6,13). Viperidae snakes are solenoglyphic, i.e, they have distinguishable inoculating fangs with ducts from which the venom is ejected through a "subterminal" orifice. When the snake is resting, the fangs lie along the upper jaw and are covered by a mucous membrane. The snake projects the front part of its body against its prey or aggressor and then the fangs move forward at the moment of the bite. They can deeply inoculate a great amount of venom, as if they were like the needle and syringe of an injection(3,8,10,38). These are the snakes best adapted for biting.
EPIDEMIOLOGY: Over 20,000 snake envenomations occur every year in Brazil and more than 80% of these accidents are caused by Bothrops(30,31). Over 2,000 cases occur annually in the state of São Paulo and about 85% of them are caused by Bothrops(36).
PHYSIOPATHOLOGY OF THE ENVENOMATION: Bothropic venom has three principal activities: a) proteolytic or necrotic activity responsible for the inflammation and necrosis in the bite site(8,38,41); b) hemorrhagic activity, produced by at least three already isolated metalloproteins which cause the outflow of blood from the capillary vessels to the interstices(1,4,26). This can cause purpura and ecchymosis in the bite site, apart from its coagulating action(19). The venom also seems to act systemically, participating in manifestations such as bleeding of the gums(7,17,24,25,40); c) coagulating activity responsible for the coagulation factor waste such as fibrinogen deficit that could cause blood incoagulability(17,38,41). Depending on the snake species, the venom activates the X factor and/or prothrombin and/or fibrinogen (thrombin-like action)(27).
CLINICAL MANIFESTATIONS: The bite caused by Bothrops snake is followed by edema of variable intensity that increases mainly on the first day(8,17,39,41). The edema shows a violet color or may be accompanied by extensive ecchymosis(38,39). Blisters can appear, mainly in cases where there is a major tissue destruction(32). Although most bites can heal without leaving sequelae(10,34,38), in some cases the damaged tissue presents necrosis which in turn can be secondarily infected. This infection generally manifests itself through abscesses that can sometimes be quite large. In these cases, functional disorders can occur or even the amputation of the affected member would be necessary. Systemically, disturbances in coagulation and bleeding commonly occur(19,33). The red blood cell counting shows leukocytosis with neutrophil preponderance with a shift to the left(38,39), which seems to be due to the acute-phase reaction(5). The presence of inflammatory signs in the bite site, and of leukocytosis with a shift to the left, both caused by the venom itself, make the diagnosis of infection difficult.
THE IMPORTANCE OF INFECTION IN BOTHROPIC ENVENOMATION: Different studies have shown that the percentage of patients who are bitten by Bothrops snakes and who develop infection in the bite site is variable and this seems to depend on the species of the snake which most frequently causes the accidents(19). The occurrence of infection is as low as 1.0% in Natal, state of Rio Grande do Norte, where envenomation caused by B. erythromelas seems to predominate(46), and as high as 15.7% in Goiânia, state of Goiás(2), where B. moojeni seems to predominate(44). In São Paulo, state of São Paulo, where envenomation caused by B. jararaca predominates, abscesses occurred in 9% among 1,984 patients(21).
Considering that over 20,000 snake envenomation cases occur every year in Brazil, that over 80% of them are caused by Bothrops(30,31) and that for calculation effects, the diverse snakes of this genus cause envenomation which frequently evolve to abscesses like those found in HVB-IB (Vital Brazil Hospital of Butantan Institute) (9%), about 1,500 cases of this complication (bothropic envenomations) may occur every year in Brazil.
BACTERIA RESPONSIBLE FOR THE INFECTION: Although the course evolution of bothropic bites is often accompanied by abscess formation, until recently very little was known about the bacteria responsible for this inflammation. In Bahia, Teixeira(45), refers to a mixed flora made up mainly of Gram-negative bacteria and also anaerobics whose participation in the process is suggested "by the physical characteristics and the odor of the purulent secretion"(45). In Rio de Janeiro, Galvão(11), found capsuled Gram-positive diplococci, Gram-positive cocci, and Trichomonas sp. in the material obtained by aspirative puncture(11). In São Paulo, Rosa et al.(37), detected Staphylococcus aureus, Streptococcus faecalis as well as also bacteria of the Clostridium genus, including C. histolyticum, in the abscesses of 14 patients (37). In São Paulo, in a first study, Jorge et al.(15) found Morganella morganii (3 cases), Proteus sp. (2 cases) and Bacterioides sp. (2 cases) in five abscesses, and in a second study(22), M. morganii (10 cases), Escherichia coli (4 cases), Proteus rettgeri (3 cases), group D estreptococci (3 cases) and Streptococcus viridans (1 case) in 15 abscesses. In Goiás, Andrade et al.(2), found mainly, M. morganii (44 cases), E. coli (20 cases), Providencia sp. (13 cases), Klebsiela sp. (10 cases), Alcaligenes sp. (9 cases), Enterobacter sp. (8 cases), S. aureus (8 cases), and S. epidermidis (7 cases) in 99 abscesses(2). In Minas Gerais, Nishioka and Silveira (28), found E. coli (5 cases), M. morganii (2 cases) and Citrobacter diversus (2 cases) in 18 abscesses.
These studies are retrospective and/or are obtained from cultures of materials from previously opened lesions, and/or are based on the results of cultures which were examined only for aerobic bacteria.
More recently, in São Paulo, in a prospective study, Jorge et al.(23) aseptically punctured the closed abscesses of 40 patients bitten by bothropic snakes, mainly B. jararaca. They performed bacterioscopy and culture for aerobic and anaerobic organisms and isolated M. morganii (23 cases), P. rettgeri (7 cases), Enterobacter sp. (4 cases), E. coli (3 cases), Citrobacter freundi (1 case), group D estreptococci (11 cases), S. aureus (2 cases), S. viridans (1 case) and Bacteroides sp. (6 cases)(23).
ORIGINS OF THE BACTERIA: Various origins for the bacteria in the site of the venomous snakebite have been considered. The victim's clothes and skin which were pierced through by the fangs of the snake, the substances applied to the region of the bite, the cutting or puncturing instruments used in the attempt to facilitate the sucking out of some of the venom and the saliva of the person who did the sucking are all possible sources of the infection. In hospitalized patients, bacteria from the hospital itself could contaminate the lesion and cause the infection.
Prospective studies have shown that the inoculating fangs of the snake pierce the victim's clothes in percentages as low as 4.3% in São Paulo and as high as 26.7% in Uberlândia (29,35,43). Although the fangs have to pass through the victim's skin before penetrating into the deep tissues, bacteria such as Streptococcus pyogenes and S. aureus, commonly found in the human skin(9), are rarely reported to be present in the abscesses(2,15,22,28). The substances applied to the bite site, the frequency that they are applied as well as the frequency that the patients lesion the bite site and try to suck out the venom are not well known in the various parts of the country. An incision or perforation at the bite site was performed in 7.7%, 8.3% and 9.6% of the cases and sucking was performed in 7.7%, 10% and 19.3% of the cases according to studies carried out in São Paulo (SP), Uberlândia (MG), and Goiânia (GO)(29,35,43), respectively.
The hypothesis that germs from the snake itself participate in the genesis of the abscesses has been enhanced by the studies of various authors who isolated potentially pathogenic bacteria from the mouth and/or from the venom of venomous snakes from various parts of the world. Group D streptococci and enterobacteria including M. morganii were found in the inoculating fangs and in the venom of large B. jararaca snakes recently captured in the state of São Paulo(16). Pathogenic bacteria such as the enterobacteria were also isolated from the venom of Crotalus durissus terrificus(12). However, envenomations by this species (Crotalus durissus terrificus) do not usually cause infection or macroscopic necrosis in the bite site(20,39). The infection can be the result of the development of the bacteria in the tissue previously injured by the venom, the bacteria itself originally coming from the snake and inoculated at the moment of the bite(10,14,19).
TREATMENT OF THE INFECTION: In Brazil, at the present time, antimicrobial agents are recommended only after the infection has been diagnosed(7,42). The choice of the drug used, however, has been made on empirical basis. The State Health Service in 1982 and the Ministry of Health, in 1987 recommended, respectively, penicillin benzatine(41) and penicillin G associated with oxacillin(7). Such antimicrobial agents do not possess the necessary amplitude against for the bacteria found in the abscesses. Based on recent studies, the use of chloramphenicol as a sole antimicrobical agent, or a combination of benzylpenicillin or ampicillin with aminoglycoside or trimethoprim/ sulfamethoxazole(18) has been recommended. This procedure has also been adopted by the State Health Service(42). Some antimicrobial agents such as cephalosporins of the second and third generations could turn out to be useful in some cases(23).
PROPHYLAXIS OF THE INFECTION: The use of an antimicrobial agent before an infection has been diagnosed has not been recommended and it would not seem sensible to apply to administer one for the prophylaxis of an infection which occurs in only about 10% of the patients, and which in most cases is restricted to the bite site(19). Prognostic factors are known, however, for the occurrence of the abscess(32). Thus, the use of antimicrobial agents should be restricted to the cases in which there is a great probability of infection. A randomized and double-blind study which is now underway evaluates whether or not this procedure reduces the occurrence of abscess after a bothropic snakebite.
01 AMORIM MF., MELLO RF., SALIBA F. Lesões renais induzidas experimentalmente no cão pelo veneno crotálico. Mem. Inst. Butantan, 1969, 34, 137-57. [ Links ]
02 ANDRADE JG., PINTO RNL., ANDRADE ALSS., MARTELLI CMT., ZICKER F. Estudo bacteriológico de abscessos causados por picada de serpentes do gênero Bothrops. Rev. Inst. Med. Trop. S. Paulo, 1989, 31, 363-7. [ Links ]
03 ANTHONY J. Anatomie de l'appareil venimeux des reptiles. In: GRASSÉ P.P. Traité de zoologie. Paris: Masson, 1970. p.549-98. [ Links ]
04 ASSAKURA MT., REICHL AP., MANDELBAUM FR. Comparison of immunological, biochemical and biophysical properties of three hemorrhagic factors isolated from the venom of Bothrops jararaca (jararaca). Toxicon, 1986, 24, 943-6. [ Links ]
05 BARRAVIERA B., LOMONTE B., TARKOWSKI A., HANSON LÅ., MEIRA DA. Acute-phase reactions, including cytokines, in patients bitten by Bothrops and Crotalus snakes in Brazil. J. Venom. Anim. Toxins, 1995, 1, 11-22. [ Links ]
06 BELLUOMINI HE. Conhecimento sobre as serpentes brasileiras e medidas de prevenção de acidentes. Rev. Bras. Saúde Ocup., 1984, 45, 82-96. [ Links ]
07 BRASIL. Ministério da Saúde. Manual de diagnóstico e tratamento de acidentes ofídicos. Brasília: Centro de Documentação do Ministério da Saúde, 1987: 49p. [ Links ]
08 BRAZIL V. A defesa contra o ophidismo. São Paulo: Pocai & Weiss, 1911: 152p.
09 COOPERSTOCK M. Indigenous flora in pathogenesis. In: FEIGIN RD, CHERRY JD., Ed. Textbook of pediatric infectious diseases. 2.ed. Philadelphia: Saunders, 1987. p.106-33. v.1. [ Links ]
10 FONSECA F. Animais peçonhentos. São Paulo: Empresa Gráfica da "Revista dos Tribunais", 1949: 376p. [ Links ]
11 GALVÃO F. O acidente botrópico. Res. Med., 1980, 9, 10-2. [ Links ]
12 GARCIA-LIMA E., LAURE CJ. A study of bacterial contamination of rattlesnake venom. Rev. Soc. Bras. Med. Trop., 1987, 20, 19-21. [ Links ]
13 HOGE AR., ROMANO-HOGE SARWL. Sinopse das serpentes peçonhentas do Brasil. Mem. Inst. Butantan, 1978/79, 42/43, 373-496. [ Links ]
14 JACKSON D. - Tratamiento cirúrgico del ofidismo. Bol. Of. Sanit. Panam., 1934, 13, 423-33. [ Links ]
15 JORGE MT., MENDONÇA JS., RIBEIRO LA., CARDOSO JLC., SILVA MLR. Bacilos Gram-negativos aeróbios em abscessos por acidente botrópico Rev. Soc. Bras. Med. Trop., 1987, 20 (supl.), 55. [ Links ]
16 JORGE MT., MENDONÇA JS., RIBEIRO LA., SILVA MLR., KUSANO EJU., CORDEIRO CLS. Flora bacteriana da cavidade oral, presas e veneno de Bothrops jararaca: possível fonte de infecção no local da picada. Rev. Inst. Med. Trop. S. Paulo, 1990, 32, 6-10. [ Links ]
17 JORGE MT., RIBEIRO LA. Acidentes por animais peçonhentos. In: AMATO NETO V., BALDY JLS. Ed. Doenças transmissíveis. 3.ed. São Paulo: Sarvier, 1989. p.133-41. [ Links ]
18 JORGE MT., RIBEIRO LA. Acidentes por peçonhentos e outros animais. In: FELIPE JUNIOR J. Ed. Pronto socorro. 2.ed. Rio de Janeiro: Guanabara Koogan, 1990: 846-52. [ Links ]
19 JORGE MT., RIBEIRO LA. Acidentes por serpentes peçonhentas do Brasil. Rev. Assoc. Med. Bras., 1990, 36, 66-77. [ Links ]
20 JORGE MT, RIBEIRO, LA. Epidemiologia e quadro clínico do acidente por cascavel sul-americana (Crotalus durissus). Rev. Inst.Med. Trop. S. Paulo, 1992, 34, 347-54. [ Links ]
21 JORGE MT., RIBEIRO LA., MENDONÇA JS. Acidente botropico: experiencia do Hospital Vital Brazil. In: CONGRESO 50º ANIVERSARIO DEL INSTITUTO DE MEDICINA TROPICAL "PEDRO KOURI" Havana, 1988. Resumenes... Cuba, Havana, 1988: 189-90. [ Links ]
22 JORGE MT., RIBEIRO LA., SILVA MLR., KUSANO EJU., MENDONÇA JS. Bacteria isolated from abscess caused by Bothrops sp. bites. In: INTERNATIONAL CONGRESS FOR INFECTIOUS DISEASES AND CONGRESSO DA SOCIEDADE BRASILEIRA DE INFECTOLOGIA, 10, Rio de Janeiro, 1988. Abstract book... Rio de Janeiro, 1988: 177. [ Links ]
23 JORGE MT., RIBEIRO LA., SILVA ML., KUSANO EJU., MENDONÇA JS. Bacteriology of abscesses complicating Bothrops snake bite in humans: a prospective study. Toxicon, 1994, 32: 743-8. [ Links ]
24 KAMIGUTI AS., THEAKSTON RDG., DESMOND H., HUTTON RA. Systemic haemorrhage in rats induced by a haemorrhagic fraction from Bothrops jararaca venom. Toxicon, 1991, 29, 1097-105. [ Links ]
25 KAMIGUTI AS., RUGMAN FP., THEAKSTON RDG., FRANÇA FOS., ISHII H., HAY CRM., BIASG. The role of venom haemorrhagin in spontaneous bleeding in Bothrops jararaca envenoming. Thromb. Haemostasis., 1992, 67, 484-8. [ Links ]
26 MANDELBAUM FR. - Isolamento e caracterização de dois fatores hemorrágicos do veneno de Bothrops jararaca. São Paulo:Escola Paulista de Medicina, l976. [Tese - doutorado]
27 NAHAS L., KAMIGUTI AS., BARROS MAR. Thrombin-like and factor X-activator components of Bothrops snake venoms. Thromb. Haemostasis, 1979, 41, 314-28. [ Links ]
28 NISHIOKA SA., SILVEIRA PVP. Bacteriology of abscesses complicanting bites of lance-headed vipers. Ann. Trop. Med. Parasitol., 1992, 86, 89-91. [ Links ]
29 PINTO RN., JORGE MT., RIBEIRO LA. Epidemiologia do acidente por serpentes venenosas em Goiás. Rev. Soc. Bras. Med. Trop., 1994, 27 (supl.1), 86. [ Links ]
30 RESENDE CC., ARAÚJO FAA., SALLENAVE RNUR. Análise epidemiológica dos acidentes ofídicos. Brasília: Ministério da Saúde, Secretaria Nacional de Ações Básicas de Saúde, 1989: 37p. [ Links ]
31 RIBEIRO LA. Epidemiology of ophidic accidents. Mem. Inst. Butantan, 1990, 52 (supl.), 15-6. [ Links ]
32 RIBEIRO LA. Fatores prognósticos para ocorrência de necrose e abscesso no envenenamento por serpente Bothrops jararaca. São Paulo:Universidade de São Paulo, Faculdade de Saúde Pública, 1996. 164p. [Tese - doutorado]
33 RIBEIRO LA., JORGE MT. Alteração da coagulação sanguínea e sangramento no acidente botrópico. Rev. Soc. Bras. Med. Trop., 1988, 21 (supl.), 120-1. [ Links ]
34 RIBEIRO LA., JORGE MT. Epidemiologia e quadro clínico dos acidentes por serpentes Bothrops jararaca adultas e filhotes. Rev. Inst. Med. Trop. S. Paulo, 1990, 32 ,436-42. [ Links ]
35 RIBEIRO LA., JORGE MT., YVERSSON LB. Epidemiologia do acidente por serpentes peçonhentas: estudo de casos atendidos em 1988. Rev. Saúde Pública, 1995, 29, 380-8. [ Links ]
36 RIBEIRO LA., PIRES DE CAMPOS VAF., ALBUQUERQUE MJ., TAKAOKA NY. Acidente ofídico no Estado de São Paulo. Rev. Assoc. Méd. Bras., 1993, 39, 4-7. [ Links ]
37 ROSA RR., IIZUKA H., HIGASHI HG., CARDOSO JLC., JORGE MT., SILVA MV. Isolamento de bactérias de lesões provocadas por picadas de ofídios. In: CONGRESSO DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL, 19, Rio de Janeiro, 1983. Programas e Resumos... Rio de Janeiro, 1983: 166. [ Links ]
38 ROSENFELD G. Acidentes por animais peçonhentos: serpentes, aranhas, escorpiões. In: VERONESI R. Ed. Doenças infecciosas e parasitárias. 8.ed. Rio de Janeiro: Guanabara Koogan, 1991: 951-62. [ Links ]
39 ROSENFELD G. Moléstias por venenos animais. Pinheiros Terapeutico, 1965, 17, 3-15. [ Links ]
40 ROSENFELD G. Symptomatology, pathology and treatment of snake bites in South America. In: BÜCHERL W., BUCKLEY E.E. Ed. Venomous animals and their venoms. New York: Academic Press, 1971: 345-84. [ Links ]
41 SÃO PAULO. Secretaria de Estado da Saúde. Instituto Butantan Manual para o diagnóstico e tratamento de acidentes por animais peçonhentos. São Paulo, 1982. [ Links ]
42 SÃO PAULO. Secretaria de Estado da Saúde. Manual de vigilância epidemiológica; acidentes por animais peçonhentos; identificação, diagnóstico e tratamento. São Paulo: Centro de Vigilância Epidemiológica" Professor Alexandre Vranjac", Instituto Butantan. Secretaria de Estado da Saúde, 1993. [ Links ]
43 SILVA CJ., RIBEIRO LA., SILVEIRA PVP., NISHIOKA SA., JORGE MT. Epidemiologia dos acidentes ofídicos em Uberlândia, MG e municípios próximos. Dados preliminares. In: CONGRESSO DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL,31, São Paulo,1995. Resumos... São Paulo, 1995: 10. [ Links ]
44 SILVA JUNIOR NJ., PINTO RNL., MOURA MR., MANSO NA., SANTOS CA. Tipos de serpentes trazidas pelos pacientes ao Hospital de Doenças Tropicais de Goiânia - GO. Rev. Soc. Bras. Med. Trop., 1988, 21 (supl.), 115. [ Links ]
45 TEIXEIRA R. Forma grave do acidente por ofídios da sub-família crotalinae. An. Acad. Med. Bahia, 1979, 2, 109-37. [ Links ]
46 WEN FH., MARINHO LAC., SILVA EP., MEDEIROS GE. Estudo retrospectivo dos acidentes botrópicos em região de alta prevalência de Bothrops erythromelas. Rev. Soc. Bras. Med. Trop., 1989, 22 (supl.), 69. [ Links ]
Received 16 October 1996.
Accepted 16 November 1996.
M. T. JORGE - Departamento de Clínica Médica, Centro de Ciências Biomédicas, Universidade Federal de Uberlândia, Avenida Pará, 1720, CEP 38.400-902, Uberlândia, Minas Gerais, Brasil.