Accepted Manuscript Do spiders vector bacteria during bites? The evidence indicates otherwise Richard S. Vetter , David L. Swanson , Scott A. Weinstein , Julian White
PII:
S0041-0101(14)00600-X
DOI:
10.1016/j.toxicon.2014.11.229
Reference:
TOXCON 4975
To appear in:
Toxicon
Received Date: 29 July 2014 Revised Date:
18 November 2014
Accepted Date: 20 November 2014
Please cite this article as: Vetter, R.S., Swanson, D.L., Weinstein, S.A., White, J., Do spiders vector bacteria during bites? The evidence indicates otherwise, Toxicon (2014), doi: 10.1016/ j.toxicon.2014.11.229. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Running Head: R. S. Vetter et al:
Send correspondence to: Rick Vetter Dept. Entomology Univ. Calif. Riverside Riverside, CA 92507 1-951-686-9858 fax 1- 951-827-3086 [email protected]
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Do spiders vector bacteria during bites? The evidence indicates otherwise
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Richard S. Vetter1,2, David L. Swanson3, Scott A. Weinstein4, and Julian White4 1
Department of Entomology, University of California, Riverside, CA 92521 USA ISCA Technologies, P.O. Box 5266, Riverside, CA 92517 USA 3 Department of Dermatology, Mayo Clinic, 13400 E. Shea Blvd., Scottsdale, AZ 85259 USA 4 Toxinology Department, Women’s & Children’s Hospital, North Adelaide SA 5006 Australia 2
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The history of clinical spider bite toxinology is filled with speculative associations and misattributions of some clinical findings to presumptive but unproven “spider bites”. This is
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particularly true for necrotic arachnidism worldwide, loxoscelism in North America and “white
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tailed spider bite” in Australia and New Zealand (Swanson and Vetter, 2005; Vetter and Isbister,
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2008; White and Weinstein, 2014). One common attribution is a purported association between
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spider bites and secondary infection.
Medical care providers frequently treat patients exhibiting cutaneous infections. Patients
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may offer histories of antecedent trauma to the skin as the source, but often there is no obvious
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cause. Occasionally, patients or their physicians speculate that a bite, especially a spider bite, is
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the etiology of the infection (Soe et al., 1987; Dominguez, 2004; Moran et al., 2006; Vetter et al.,
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2006a; El Fakih et al., 2008; Arora and Raza, 2011; Suchard, 2011). However, this speculation
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begs the question of whether spiders are capable of vectoring human pathogens or even can
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provoke an infection through a break in the skin. Although experimental work has suggested that
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this is tenable, extrapolations from those observations to validate clinical diagnoses of infection
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appear to be putting the proverbial cart before the horse. We present here a discussion of the
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evidence regarding the association between human bacterial pathogens and spider bites, and the
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likelihood that bacterial infections are spider-vectored. We show that the evidence for spider-
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vectored infection is meager, and the mere presence of bacteria on spider fangs or mouthparts
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does not predicate spiders as vectors.
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Clostridium spp. were reported in the venom and on the mouthparts of a small percentage
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of South American recluse (Loxosceles) spiders (Monteiro et al., 2002; Catalán et al., 2010).
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Subsequently, C. perfringens acted as a synergist, increasing dermonecrotic lesion size when
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concomitantly injected with Loxosceles venom into experimental rabbits (Catalán et al., 2010).
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Although a mechanism is suggested where Loxosceles bites could vector these bacteria, there is
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no proof that Clostridium actually enhances clinical dermonecrotic manifestations of cutaneous
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loxoscelism in humans nor has been isolated from such lesions. Likewise, conjecture circulated that Mycobacterium ulcerans played a contributory role
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in necrotic arachnidism in Australia because of clinical similarity to infection. However, this
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was demonstrated to be highly improbable because the bacterium does not readily survive on
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purposefully contaminated spider fangs and mouthparts and is not readily transferred in
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simulated bites (Atkinson et al., 1995). A more likely scenario is that M. ulcerans infection,
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contracted in a more conventional way and presenting as local ulceration, was misdiagnosed as
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necrotic arachnidism when this spurious diagnosis was popular amongst both medical
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professionals and the media (Harvey and Raven, 1991; Hayman and Smith, 1991). Spider bite is
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not currently listed as a vector for M. ulcerans infection (Merritt et al., 2010).
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Ahrens and Crocker (2011) surveyed black widow (Latrodectus) fangs for bacteria and
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generated a list of potential pathogens. The authors postulated that widow envenomation could
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lead to necrotic arachnidism through a mechanism of cutaneous infection by bacteria. However,
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in overwhelming contradiction, published documentations of 3,245 Latrodectus bite diagnoses
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worldwide show no evidence of bacterial infection as part of widow envenomation syndrome
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(Table 1) nor have Latrodectus spiders ever been associated with necrotic arachnidism.
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Mascarelli et al. (2013) attempted to associate woodlouse spiders, Dysdera crocata, with
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Bartonella henselae infection in a mother and two children. The authors readily admitted that 1)
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no spiders were seen inflicting bites and were merely implicated by their presence, 2) the
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presumptive bites may have had nothing to do with the infection, and 3) finding Bartonella DNA
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in the spider may have only been coincidental. Also mentioned is that the family dog, albeit
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seronegative, had a flea infestation and slept on the mother’s bed. Multiple patients in the same
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family showing the same medical malady is an indicator that spiders are not involved (Vetter et
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al., 2006a) and that a hematophagous arthropod or infectious etiology should be considered
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instead. The wounds shown in the article are typical blood sucking injuries.
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If infection were part of spider bite syndrome, it should be obvious, common and a
routinely reported manifestation of envenomation. Publications describing clinical spider bites
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are plentiful in the medical literature, and include large case series documenting the spectrum of
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signs and symptoms in humans. Such series involve medically important spiders of the genera
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Latrodectus (widow spiders), Loxosceles (recluse spiders), Phoneutria (Brazilian wandering or
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armed spiders), Atrax/Hadronyche (Australian funnel web spiders) as well as general spider
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envenomations encompassing a plethora of species, and four studies exonerating specific genera
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as etiologies of necrotic arachnidism (Table 1). Twenty-one studies documented in Table 1
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involving 4,613 bite diagnoses and verified bites give no mention of infections. These include
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one study of 167 verified bites of red-back spiders (Latrodectus hasselti) listing 41 non-
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infectious clinical features (Wiener, 1961), a second study involving 45 verified South African
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Latrodectus bites or strong pathognomonic latrodectism cases (L. indistinctus, L. geometricus)
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listing 22 non-infectious signs and symptoms (Müller, 1993) and another of 19 verified brown
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recluse spider bites (Sams et al., 2001). Isbister and Gray (2002) reported an infection rate of
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0.9% in 750 verified bites, although the infections were non-confirmed and based on nonspecific
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findings of redness, swelling and pain. Málaque et al. (2002) simply reported that infection is
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rare (3%) and mild in loxoscelism. The study by Sezerino et al. (1998) involved retrospective
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analysis of loxoscelism cases and stated nothing more instructive than “18% secondary
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infections” listed as a line in a table; a spider was verified in only 2.6% of the cases, making this
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outlier result difficult to interpret, as well as loxoscelism being historically fraught with many
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misdiagnoses (Anderson, 1998; Vetter, 2008).
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The late Phillip Anderson, American dermatologist and loxoscelism expert in the latter portion of the 20th Century, stated that he and his colleagues treated about 1,000 credible
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loxoscelism cases, mostly referrals (i.e., the more extreme cases), and “never encountered an
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infected bite, even in unmedicated patients.” He further noted that recluse bites are “not
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exudative” (Anderson, 1998). Rader et al. (2012) recently offered a diagnostic algorithm where
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“pus observed in lesion” is the first negative exam feature that removes recluse spider bite from
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the prioritized differential diagnosis.
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MRSA (methicillin-resistant Staphylococcus aureus) has become a worldwide pandemic in recent years, and has been frequently misdiagnosed as spider bite (Dominguez, 2004; Miller
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and Spellberg, 2004; Moran et al., 2006; Vetter et al., 2006a; Cohen, 2007; El Fakih et al., 2008;
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Arora and Raza, 2011). It has also been speculated, without supportive evidence, to be spider-
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vectored (Fagan et al., 2003); this speculation was soundly criticized (Miller and Spellberg,
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2004; Suchard, 2011). Baxtrom et al. (2006) sampled 100 common household spiders from
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Illinois (USA). From cultures of external and internal microbial fauna, they detected 11 taxa of
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bacteria, none being MRSA, and only one human pathogen: Aeromonas spp., a primarily
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gastrointestinal pathogen which may occasionally cause soft tissue infection, most often after
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trauma and exposure to a contaminated aquatic source (Janda and Abbott 2010; SAW pers. obs.)
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but has no clinical or basic biomedical association with spider bites. In the Pacific Northwest of
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North America, hobo spiders (Eratigena (=Tegenaria) agrestis) were originally implicated in
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necrotic skin lesions, but currently their venom toxicity is in question (Binford, 2001; Vetter and
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Isbister, 2004; McKeown et al., 2014). A recent study investigating the possibility of bacterial
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synergism in hobo spider bites documented eight strains of external and internal microbial fauna,
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none being pathogenic (Gaver-Wainwright et al., 2011). Furthermore, when hobo spiders were
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exposed to MRSA in petri dishes for 5 minutes, no MRSA bacteria were found on the spiders
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afterward nor did they transfer MRSA to clean surfaces upon which they were placed (Gaver-
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Wainwright et al., 2011).
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A spider bite with its infusion of venom is not analogous to a contaminated break in human epidermis from a random cut or abrasion antecedent to infection. In fact, spider venoms
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(and venoms from other animals, i.e., snakes, bees, wasps, scorpions) are known to have
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antibacterial properties (Stocker and Traynor, 1986; Talan et al., 1991; Yan and Adams, 1998;
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Haeberli et al., 2000; Corzo et al., 2001, 2002; Kuhn-Nentwig et al., 2002; Budnik et al., 2004;
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Kozlov et al., 2006; Benli and Yigit, 2008; Harrison et al., 2014; Jalaei et al., 2014) and were
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subject to investigation in hope of discovering novel antibacterial therapeutics. Venom from two
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spiders inhibited growth of Staphylococcus aureus (Corzo et al., 2002; Benli and Yigit, 2008).
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Kozlov et al. (2006) calculated that a bite from the spider Lachesana tarabaevi introduced
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sufficient venom into a prey to clear all potential bacterial contaminants. Speculation on an
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evolutionary function of venom is protection of the spider from bacterial contamination from its
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food. Spider venom toxins are increasingly being reported as potential lead substances for the
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development of novel antibacterial agents (Saez et al., 2010; Tan et al., 2013).
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An important advancement in spider bite diagnosis in recent years is the realization that
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bacterial infections have been commonly misattributed as spider envenomation by both
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physicians and patients (Soe et al., 1987; Dominguez, 2004; Isbister, 2004; Swanson and Vetter,
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2005; Moran et al., 2006; Vetter et al., 2006a; Cohen, 2007; El Fakih et al., 2008; Vetter, 2008;
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Arora and Raza, 2011; Suchard, 2011), where “spider bite” is used as a default diagnosis despite
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lack of supporting evidence (Miller and Spellberg, 2004; Suchard, 2011). Of 182 southern
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Californian patients presenting with complaint of spider bite, only 3.8% had spider
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envenomations, while 85.7% had cutaneous infections (Suchard, 2011). In a national study, 29%
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of 248 patients with confirmed etiologies of MRSA for their skin-and-soft-tissue lesions
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presented for spider bites (Moran et al., 2006). Cohen (2007) states that abscess, with or without
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cellulitis, is the most common clinical presentation of community-acquired MRSA and that,
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although bacterial vectoring by spiders or insects is an occasional possibility, “it is far more
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likely that most, if not all, of the lesions are primary CAMRSA cutaneous infections.” The only
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credible report of spider bite leading to infection of which we are aware was one episode
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involving an Australian golden silk spider, a very large orbweaver of the genus Nephila, which
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resulted in colonization by the bacteria Photorhabdus luminescens, a common nematode-
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colonizing insecticidal bacterium rarely found in humans (Peel et al., 1999). The bite led to a
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purulent lesion that persisted over 2 months.
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Although spider bite may be an attractive and tenable causative agent of a bacterial
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infection, this etiology is highly improbable. We believe any implied causative association
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between cutaneous infections and spider bites should be considered suspect, and that the medical
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community should not rely on spiders as the scapegoats for bacterial infections. Placing blame
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on spiders as the etiology for idiopathic wounds reinforces a prejudice that can have unwarranted
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post-incident fallout once a patient leaves the physician’s care (e.g., immediate heightened
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anxiety, overzealous application of insecticides) (Vetter and Isbister, 2008). At the present time,
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it appears that the often-errantly assigned spider-bacteria connection is yet another myth that has
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been erroneously proliferating in the clinical toxinology and general medicine community.
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Conflict of Interest: The authors declare that there are no conflicts of interest.
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Acknowledgment
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We thank Serguei Triapitsyn (Univ. Calif. Riverside) for translating the Krasnonos et al. article
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into English.
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Ribeiro, L.A., Jorge, M.T., Piesco, R.V., Nishioka, S. D., 1990. Wolf spider bites in São Paulo, Brazil: a clinical and epidemiological study of 515 cases. Toxicon 28, 715-717.
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Saez, N.J., Senff, S., Jensen, J.E., Er, S.Y., Herzig, V., Rash, L.D., King, G.F., 2010. Spidervenom peptides as therapeutics. Toxins (Basel) 2, 2851-2871. Sams, H.H., Hearth, S.B., Long, L.L., Wilson, D.C., Sanders, D.H., King, L.E. Jr., 2001.
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Nineteen documented cases of Loxosceles reclusa envenomation. J. Am. Acad. Dermatol.
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44, 603-608.
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Sezerino, U.M., Zannin, M., Coelho, L.K., Gonçalves, J. Jr., Grando, M., Mattosinho, S.G., Cardoso, J.L.C., von Eickstedt, V.R., França, F.O.S., Barbaro, K.C., Fan. H.W., 1998. A
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clinical and epidemiological study of Loxosceles spider envenoming in Santa Catarina,
307
Brazil. Trans. Roy. Soc. Trop. Med. Hyg. 92, 546-548.
311 312 313 314 315 316 317 318
Stocker, J.F., Traynor, J.R., 1986. The action of various venoms on Escherichia coli. J. Appl.
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with joystick mimicking a spider bite. West. J. Med. 146, 748.
Bacteriol. 61, 383-388.
Suchard, J.R., 2011. Spider bite” lesions are usually diagnosed as skin and soft-tissue
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Soe, D.B., Gersten, L.M., Wilkins, J., Patzakis, M.J., Harvey, J.P., 1987. Infection associated
infections. J. Emerg. Med. 41, 473-481.
Sutherland, S.K., Trinca, J.C., 1978. Survey of 2144 cases of red-back spider bites. Med. J. Austral. 2, 620-623.
Swanson, D.L., Vetter, R.S., 2005. Bites of brown recluse spiders and suspected necrotic
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arachnidism. New Engl. J. Med. 352, 700-707. Talan, D.A., Citron, D.M., Overturf, G.D., Singer, B., Froman, P., Goldstein, J.C., 1991. Antibacterial activity of crotalid venoms against oral snake flora and other clinical bacteria.
320
J. Infect. Dis. 164, 195-198.
Tan, H., Ding, X., Meng, S., Liu, C., Wang, H., Xia, L., Liu, Z., Liang, S., 2013. Antimicrobial
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potenital of lycosin-I, a cationic and amphiphilic peptide from the venom fo the spider
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Lycosa singorensis. Curr. Molec. Med. 13, 900-910.
324
Vetter, R.S., 2008. Spiders of the genus Loxosceles (Araneae: Sicariidae): a review of biological,
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medical and psychological aspects regarding envenomations. J. Arachnol. 36, 150-163.
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Vetter, R.S., Isbister, G.K., 2004. Do hobo spider bites cause dermonecrotic injuries? Ann. Emerg. Med. 44, 605-607. Vetter, R.S., Isbister, G.K., 2008. Medical aspects of spider bites. Ann. Rev. Entomol. 53, 409429.
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Vetter, R.S., Pagac, B.B., Reiland, R.W., Bolesh D.T., Swanson, D.L., 2006a. Skin lesions in barracks: consider community-acquired methicillin-resistant Staphylococcus aureus
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infection instead of spider bites. Military Med. 171, 830-832.
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Vetter, R.S., Isbister, G.K., Bush, S.P., Boutin, L.J., 2006b. Verified bites by Cheiracanthium spiders in the United States and Australia: where is the necrosis? Amer. J. Trop. Med. Hyg.
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74, 1043-1048.
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White J., Weinstein S.A., 2014. A phoenix of clinical toxinology: White-tailed spider (Lampona spp.) bites. A case report and review of medical significance. Toxicon 87, 76-80.
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White, J., Hirst, D., Hender, E., 1989. 36 cases of bites by spiders, including the white-tailed
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Wiener, S., 1961. Red back spider bite in Australia: an analysis of 167 cases. Med. J. Austral. 2, 44-49.
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spider, Lampona cylindrata. Med. J. Austral. 150, 401-403.
Wright, S.W., Wrenn, K.D., Murray, L., Seger, D., 1997. Clinical presentation and outcome of brown recluse spider bite. Ann. Emerg. Med. 30, 28-32.
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Yan, L., Adams, M.E., 1998. Lycotoxins, antimicrobial peptides from venom of the wolf spider Lycosa carolinensis. J. Biol. Chem. 273, 2059-2066.
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Table 1. Studies of series of spider bite diagnoses and its association, or lack thereof, with bacterial infections. Some studies were
348
performed retrospectively and, hence, the most appropriate designation is “bite diagnoses” rather than “spider bite” as these could
349
have been misdiagnoses with non-spider etiologies. DX = diagnoses.
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Spider (genus)
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Country
Comment
Widow (Latrodectus)
2,144
Australia
no mention of infection
353
Widow (Latrodectus)
167
Australia
354
Widow (Latrodectus)
561,2
Australia
355
Widow (Latrodectus)
163
USA
356
Widow (Latrodectus)
52
357
Widow (Latrodectus)
358
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# of DX
Reference
Sutherland and Trinca 1978 Wiener 1961
no mention of infection
Isbister and Gray 2002
no mention of infection
Clark et al. 1992
USA
no mention of infection
Frawley and Ginsburg 1935
42
USA
no mention of infection
Ginsburg 1937
Widow (Latrodectus)
25
USA
no mention of infection
Kirby-Smith 1942
359
Widow (Latrodectus)
463
Uzbekistan
no mention of infection
Krasnonos et al. 1989
360
Widow (Latrodectus)
56
Iran
no mention of infection
Afshari et al. 2009
361
Widow (Latrodectus)
32
Croatia
no mention of infection
Dzelalija et al. 2003
362
Widow (Latrodectus)
45
South Africa
no mention of infection
Müller 1993
363
Recluse (Loxosceles)
359
Brazil
3% mild local infection
Málaque et al. 2002
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no mention of infection
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Recluse (Loxosceles)
267
Brazil
18% secondary infection
Sezerino et al. 1998
365
Recluse (Loxosceles)
111
USA
no mention of infection
Wright et al. 1997
366
Recluse (Loxosceles)
192
USA
no mention of infection
Sams et al. 2001
367
Armed (Phoneutria)
422
Brazil
no mention of infection
Bucaretchi et al. 2000
368
Wolf (Scaptocosa)
515
Brazil
no mention of infection
Ribeiro et al. 1990
369
Australian Funnel Web
198
Australia
no mention of infection
Isbister et al. 2005
370
(Atrax/Hadronyche)
371
Yellow sac (Cheiracanthium)
202,3
USA/Australia
no cases of confirmed infections
Vetter et al. 2006b
372
General (many species)
362
Australia
no mention of infection
White et al. 1989
373
General (many species)
142
Switzerland
no mention of infection
Nentwig et al. 2013
374
General (many species)
332
USA
no mention of infection
McKeown et al. 2014
375
General (many species)
7502
Australia
7 patients with infection
Isbister and Gray 2002
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376
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(redness, pain, no mention of pus)
377
White-tail (Lampona)
1304
Australia
no cases of confirmed infection
Isbister and Gray 2003
378
Black house (Badumna)
254
Australia
no cases of confirmed infection
Isbister and Gray 2004
379 380
1
- a subset of the 750 verified Australian bite series recorded by Isbister and Gray 2002
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381
2
382
3
- ten of these Cheiracanthium bites were a subset from the 750 verified Australian bite series
383
4
- bites from white-tail and black house spiders were part of the 750 Australian bite series but they are repeated here because these
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spiders were wrongly implicated in necrotic skin lesions
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- verified bite reports with offending spider identified by an arachnologist or knowledgable physician
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TOXCON 14-323 bullet points
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Spiders have often been viewed as tenable vectors of bacterial infections Review of the spider bite literature lacks evidence of infectious sequelae Spiders are unlikely vectors of bacterial transmission to humans when they bite Physicians should not casually associate bacterial infection with spider bites
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• • • •
PII:
S0041-0101(14)00600-X
DOI:
10.1016/j.toxicon.2014.11.229
Reference:
TOXCON 4975
To appear in:
Toxicon
Received Date: 29 July 2014 Revised Date:
18 November 2014
Accepted Date: 20 November 2014
Please cite this article as: Vetter, R.S., Swanson, D.L., Weinstein, S.A., White, J., Do spiders vector bacteria during bites? The evidence indicates otherwise, Toxicon (2014), doi: 10.1016/ j.toxicon.2014.11.229. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Running Head: R. S. Vetter et al:
Send correspondence to: Rick Vetter Dept. Entomology Univ. Calif. Riverside Riverside, CA 92507 1-951-686-9858 fax 1- 951-827-3086 [email protected]
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11/20/14 11:39 PM
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For Publication in: Toxicon - Editorial
Do spiders vector bacteria during bites? The evidence indicates otherwise
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Richard S. Vetter1,2, David L. Swanson3, Scott A. Weinstein4, and Julian White4 1
Department of Entomology, University of California, Riverside, CA 92521 USA ISCA Technologies, P.O. Box 5266, Riverside, CA 92517 USA 3 Department of Dermatology, Mayo Clinic, 13400 E. Shea Blvd., Scottsdale, AZ 85259 USA 4 Toxinology Department, Women’s & Children’s Hospital, North Adelaide SA 5006 Australia 2
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original word count: 2369
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The history of clinical spider bite toxinology is filled with speculative associations and misattributions of some clinical findings to presumptive but unproven “spider bites”. This is
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particularly true for necrotic arachnidism worldwide, loxoscelism in North America and “white
35
tailed spider bite” in Australia and New Zealand (Swanson and Vetter, 2005; Vetter and Isbister,
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2008; White and Weinstein, 2014). One common attribution is a purported association between
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spider bites and secondary infection.
Medical care providers frequently treat patients exhibiting cutaneous infections. Patients
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may offer histories of antecedent trauma to the skin as the source, but often there is no obvious
40
cause. Occasionally, patients or their physicians speculate that a bite, especially a spider bite, is
41
the etiology of the infection (Soe et al., 1987; Dominguez, 2004; Moran et al., 2006; Vetter et al.,
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2006a; El Fakih et al., 2008; Arora and Raza, 2011; Suchard, 2011). However, this speculation
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begs the question of whether spiders are capable of vectoring human pathogens or even can
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provoke an infection through a break in the skin. Although experimental work has suggested that
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this is tenable, extrapolations from those observations to validate clinical diagnoses of infection
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appear to be putting the proverbial cart before the horse. We present here a discussion of the
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evidence regarding the association between human bacterial pathogens and spider bites, and the
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likelihood that bacterial infections are spider-vectored. We show that the evidence for spider-
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vectored infection is meager, and the mere presence of bacteria on spider fangs or mouthparts
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does not predicate spiders as vectors.
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Clostridium spp. were reported in the venom and on the mouthparts of a small percentage
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of South American recluse (Loxosceles) spiders (Monteiro et al., 2002; Catalán et al., 2010).
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Subsequently, C. perfringens acted as a synergist, increasing dermonecrotic lesion size when
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concomitantly injected with Loxosceles venom into experimental rabbits (Catalán et al., 2010).
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Although a mechanism is suggested where Loxosceles bites could vector these bacteria, there is
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no proof that Clostridium actually enhances clinical dermonecrotic manifestations of cutaneous
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loxoscelism in humans nor has been isolated from such lesions. Likewise, conjecture circulated that Mycobacterium ulcerans played a contributory role
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in necrotic arachnidism in Australia because of clinical similarity to infection. However, this
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was demonstrated to be highly improbable because the bacterium does not readily survive on
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purposefully contaminated spider fangs and mouthparts and is not readily transferred in
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simulated bites (Atkinson et al., 1995). A more likely scenario is that M. ulcerans infection,
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contracted in a more conventional way and presenting as local ulceration, was misdiagnosed as
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necrotic arachnidism when this spurious diagnosis was popular amongst both medical
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professionals and the media (Harvey and Raven, 1991; Hayman and Smith, 1991). Spider bite is
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not currently listed as a vector for M. ulcerans infection (Merritt et al., 2010).
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Ahrens and Crocker (2011) surveyed black widow (Latrodectus) fangs for bacteria and
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generated a list of potential pathogens. The authors postulated that widow envenomation could
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lead to necrotic arachnidism through a mechanism of cutaneous infection by bacteria. However,
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in overwhelming contradiction, published documentations of 3,245 Latrodectus bite diagnoses
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worldwide show no evidence of bacterial infection as part of widow envenomation syndrome
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(Table 1) nor have Latrodectus spiders ever been associated with necrotic arachnidism.
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Mascarelli et al. (2013) attempted to associate woodlouse spiders, Dysdera crocata, with
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Bartonella henselae infection in a mother and two children. The authors readily admitted that 1)
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no spiders were seen inflicting bites and were merely implicated by their presence, 2) the
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presumptive bites may have had nothing to do with the infection, and 3) finding Bartonella DNA
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in the spider may have only been coincidental. Also mentioned is that the family dog, albeit
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seronegative, had a flea infestation and slept on the mother’s bed. Multiple patients in the same
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family showing the same medical malady is an indicator that spiders are not involved (Vetter et
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al., 2006a) and that a hematophagous arthropod or infectious etiology should be considered
81
instead. The wounds shown in the article are typical blood sucking injuries.
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If infection were part of spider bite syndrome, it should be obvious, common and a
routinely reported manifestation of envenomation. Publications describing clinical spider bites
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are plentiful in the medical literature, and include large case series documenting the spectrum of
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signs and symptoms in humans. Such series involve medically important spiders of the genera
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Latrodectus (widow spiders), Loxosceles (recluse spiders), Phoneutria (Brazilian wandering or
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armed spiders), Atrax/Hadronyche (Australian funnel web spiders) as well as general spider
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envenomations encompassing a plethora of species, and four studies exonerating specific genera
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as etiologies of necrotic arachnidism (Table 1). Twenty-one studies documented in Table 1
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involving 4,613 bite diagnoses and verified bites give no mention of infections. These include
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one study of 167 verified bites of red-back spiders (Latrodectus hasselti) listing 41 non-
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infectious clinical features (Wiener, 1961), a second study involving 45 verified South African
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Latrodectus bites or strong pathognomonic latrodectism cases (L. indistinctus, L. geometricus)
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listing 22 non-infectious signs and symptoms (Müller, 1993) and another of 19 verified brown
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recluse spider bites (Sams et al., 2001). Isbister and Gray (2002) reported an infection rate of
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0.9% in 750 verified bites, although the infections were non-confirmed and based on nonspecific
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findings of redness, swelling and pain. Málaque et al. (2002) simply reported that infection is
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rare (3%) and mild in loxoscelism. The study by Sezerino et al. (1998) involved retrospective
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analysis of loxoscelism cases and stated nothing more instructive than “18% secondary
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infections” listed as a line in a table; a spider was verified in only 2.6% of the cases, making this
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outlier result difficult to interpret, as well as loxoscelism being historically fraught with many
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misdiagnoses (Anderson, 1998; Vetter, 2008).
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The late Phillip Anderson, American dermatologist and loxoscelism expert in the latter portion of the 20th Century, stated that he and his colleagues treated about 1,000 credible
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loxoscelism cases, mostly referrals (i.e., the more extreme cases), and “never encountered an
106
infected bite, even in unmedicated patients.” He further noted that recluse bites are “not
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exudative” (Anderson, 1998). Rader et al. (2012) recently offered a diagnostic algorithm where
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“pus observed in lesion” is the first negative exam feature that removes recluse spider bite from
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the prioritized differential diagnosis.
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MRSA (methicillin-resistant Staphylococcus aureus) has become a worldwide pandemic in recent years, and has been frequently misdiagnosed as spider bite (Dominguez, 2004; Miller
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and Spellberg, 2004; Moran et al., 2006; Vetter et al., 2006a; Cohen, 2007; El Fakih et al., 2008;
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Arora and Raza, 2011). It has also been speculated, without supportive evidence, to be spider-
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vectored (Fagan et al., 2003); this speculation was soundly criticized (Miller and Spellberg,
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2004; Suchard, 2011). Baxtrom et al. (2006) sampled 100 common household spiders from
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Illinois (USA). From cultures of external and internal microbial fauna, they detected 11 taxa of
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bacteria, none being MRSA, and only one human pathogen: Aeromonas spp., a primarily
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gastrointestinal pathogen which may occasionally cause soft tissue infection, most often after
119
trauma and exposure to a contaminated aquatic source (Janda and Abbott 2010; SAW pers. obs.)
120
but has no clinical or basic biomedical association with spider bites. In the Pacific Northwest of
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North America, hobo spiders (Eratigena (=Tegenaria) agrestis) were originally implicated in
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necrotic skin lesions, but currently their venom toxicity is in question (Binford, 2001; Vetter and
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Isbister, 2004; McKeown et al., 2014). A recent study investigating the possibility of bacterial
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synergism in hobo spider bites documented eight strains of external and internal microbial fauna,
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none being pathogenic (Gaver-Wainwright et al., 2011). Furthermore, when hobo spiders were
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exposed to MRSA in petri dishes for 5 minutes, no MRSA bacteria were found on the spiders
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afterward nor did they transfer MRSA to clean surfaces upon which they were placed (Gaver-
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Wainwright et al., 2011).
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A spider bite with its infusion of venom is not analogous to a contaminated break in human epidermis from a random cut or abrasion antecedent to infection. In fact, spider venoms
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(and venoms from other animals, i.e., snakes, bees, wasps, scorpions) are known to have
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antibacterial properties (Stocker and Traynor, 1986; Talan et al., 1991; Yan and Adams, 1998;
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Haeberli et al., 2000; Corzo et al., 2001, 2002; Kuhn-Nentwig et al., 2002; Budnik et al., 2004;
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Kozlov et al., 2006; Benli and Yigit, 2008; Harrison et al., 2014; Jalaei et al., 2014) and were
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subject to investigation in hope of discovering novel antibacterial therapeutics. Venom from two
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spiders inhibited growth of Staphylococcus aureus (Corzo et al., 2002; Benli and Yigit, 2008).
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Kozlov et al. (2006) calculated that a bite from the spider Lachesana tarabaevi introduced
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sufficient venom into a prey to clear all potential bacterial contaminants. Speculation on an
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evolutionary function of venom is protection of the spider from bacterial contamination from its
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food. Spider venom toxins are increasingly being reported as potential lead substances for the
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development of novel antibacterial agents (Saez et al., 2010; Tan et al., 2013).
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An important advancement in spider bite diagnosis in recent years is the realization that
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bacterial infections have been commonly misattributed as spider envenomation by both
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physicians and patients (Soe et al., 1987; Dominguez, 2004; Isbister, 2004; Swanson and Vetter,
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2005; Moran et al., 2006; Vetter et al., 2006a; Cohen, 2007; El Fakih et al., 2008; Vetter, 2008;
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Arora and Raza, 2011; Suchard, 2011), where “spider bite” is used as a default diagnosis despite
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lack of supporting evidence (Miller and Spellberg, 2004; Suchard, 2011). Of 182 southern
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Californian patients presenting with complaint of spider bite, only 3.8% had spider
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envenomations, while 85.7% had cutaneous infections (Suchard, 2011). In a national study, 29%
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of 248 patients with confirmed etiologies of MRSA for their skin-and-soft-tissue lesions
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presented for spider bites (Moran et al., 2006). Cohen (2007) states that abscess, with or without
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cellulitis, is the most common clinical presentation of community-acquired MRSA and that,
153
although bacterial vectoring by spiders or insects is an occasional possibility, “it is far more
154
likely that most, if not all, of the lesions are primary CAMRSA cutaneous infections.” The only
155
credible report of spider bite leading to infection of which we are aware was one episode
156
involving an Australian golden silk spider, a very large orbweaver of the genus Nephila, which
157
resulted in colonization by the bacteria Photorhabdus luminescens, a common nematode-
158
colonizing insecticidal bacterium rarely found in humans (Peel et al., 1999). The bite led to a
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purulent lesion that persisted over 2 months.
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Although spider bite may be an attractive and tenable causative agent of a bacterial
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infection, this etiology is highly improbable. We believe any implied causative association
162
between cutaneous infections and spider bites should be considered suspect, and that the medical
163
community should not rely on spiders as the scapegoats for bacterial infections. Placing blame
164
on spiders as the etiology for idiopathic wounds reinforces a prejudice that can have unwarranted
165
post-incident fallout once a patient leaves the physician’s care (e.g., immediate heightened
166
anxiety, overzealous application of insecticides) (Vetter and Isbister, 2008). At the present time,
167
it appears that the often-errantly assigned spider-bacteria connection is yet another myth that has
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been erroneously proliferating in the clinical toxinology and general medicine community.
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Conflict of Interest: The authors declare that there are no conflicts of interest.
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Acknowledgment
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We thank Serguei Triapitsyn (Univ. Calif. Riverside) for translating the Krasnonos et al. article
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into English.
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References
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Afshari, R., Khadem-Rezaiyan, M., Balali-Mood, M., 2009. Spider bite (latrodectism) in
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Ahrens, B., Crocker, C., 2011. Bacterial etiology of necrotic arachnidism in black widow spider bites. J. Clin. Toxicol. 1:106. doi:10.4172/2161-0495.1000106
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Binford, G.J., 2001. An analysis of geographic and intersexual chemical variation in venoms of
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R.J., 2000. A clinico-epidemiological study of bites by spiders of the genus Phoneutria.
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Grishin, E.V., Zubarev, R.A., 2004. De novo sequencing of antimicrobial peptides isolated
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of Loxosceles laeta: Its implication in loxoscelism treatment. Toxicon 56, 890-897.
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Table 1. Studies of series of spider bite diagnoses and its association, or lack thereof, with bacterial infections. Some studies were
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performed retrospectively and, hence, the most appropriate designation is “bite diagnoses” rather than “spider bite” as these could
349
have been misdiagnoses with non-spider etiologies. DX = diagnoses.
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Spider (genus)
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Country
Comment
Widow (Latrodectus)
2,144
Australia
no mention of infection
353
Widow (Latrodectus)
167
Australia
354
Widow (Latrodectus)
561,2
Australia
355
Widow (Latrodectus)
163
USA
356
Widow (Latrodectus)
52
357
Widow (Latrodectus)
358
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Reference
Sutherland and Trinca 1978 Wiener 1961
no mention of infection
Isbister and Gray 2002
no mention of infection
Clark et al. 1992
USA
no mention of infection
Frawley and Ginsburg 1935
42
USA
no mention of infection
Ginsburg 1937
Widow (Latrodectus)
25
USA
no mention of infection
Kirby-Smith 1942
359
Widow (Latrodectus)
463
Uzbekistan
no mention of infection
Krasnonos et al. 1989
360
Widow (Latrodectus)
56
Iran
no mention of infection
Afshari et al. 2009
361
Widow (Latrodectus)
32
Croatia
no mention of infection
Dzelalija et al. 2003
362
Widow (Latrodectus)
45
South Africa
no mention of infection
Müller 1993
363
Recluse (Loxosceles)
359
Brazil
3% mild local infection
Málaque et al. 2002
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no mention of infection
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Recluse (Loxosceles)
267
Brazil
18% secondary infection
Sezerino et al. 1998
365
Recluse (Loxosceles)
111
USA
no mention of infection
Wright et al. 1997
366
Recluse (Loxosceles)
192
USA
no mention of infection
Sams et al. 2001
367
Armed (Phoneutria)
422
Brazil
no mention of infection
Bucaretchi et al. 2000
368
Wolf (Scaptocosa)
515
Brazil
no mention of infection
Ribeiro et al. 1990
369
Australian Funnel Web
198
Australia
no mention of infection
Isbister et al. 2005
370
(Atrax/Hadronyche)
371
Yellow sac (Cheiracanthium)
202,3
USA/Australia
no cases of confirmed infections
Vetter et al. 2006b
372
General (many species)
362
Australia
no mention of infection
White et al. 1989
373
General (many species)
142
Switzerland
no mention of infection
Nentwig et al. 2013
374
General (many species)
332
USA
no mention of infection
McKeown et al. 2014
375
General (many species)
7502
Australia
7 patients with infection
Isbister and Gray 2002
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(redness, pain, no mention of pus)
377
White-tail (Lampona)
1304
Australia
no cases of confirmed infection
Isbister and Gray 2003
378
Black house (Badumna)
254
Australia
no cases of confirmed infection
Isbister and Gray 2004
379 380
1
- a subset of the 750 verified Australian bite series recorded by Isbister and Gray 2002
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2
382
3
- ten of these Cheiracanthium bites were a subset from the 750 verified Australian bite series
383
4
- bites from white-tail and black house spiders were part of the 750 Australian bite series but they are repeated here because these
384
spiders were wrongly implicated in necrotic skin lesions
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- verified bite reports with offending spider identified by an arachnologist or knowledgable physician
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TOXCON 14-323 bullet points
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Spiders have often been viewed as tenable vectors of bacterial infections Review of the spider bite literature lacks evidence of infectious sequelae Spiders are unlikely vectors of bacterial transmission to humans when they bite Physicians should not casually associate bacterial infection with spider bites
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