Squirrel fibromatosis vs. bot fly infestation:

Exposure & transmission

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FIBROMATOSIS       How squirrels contract fibromatosis in nature is presently unknown. However, evidence from laboratory studies indicates that fibroma virus is transmitted to uninfected squirrels by the injection of suspensions of, or blood from, fibroma tissue from an infected animal (Kilham et al., 1953; Kilham, 1955; Kirschstein et al., 1958; Hirth et al. 1969; Fig. 1).

Fig. 1: Immature eastern gray squirrel (66 days old) that had been injected with fibroma virus 38 days previously; note large, necrotic fibromas in the hip region where inoculation occurred. [b&w photo from Kilham (1955); by permission of Oxford University Press]

Mosquitoes probably accomplish this in nature (that is, they are likely 'vectors' of this virus), as these have been shown to transmit the fibroma virus in a laboratory study (Kilham, 1955). Both species tested (the yellowfever mosquito, Aedes aegypti, and the common malaria mosquito, Anopheles quadrimaculatus) were capable of transmission.

      Whether this virus can spread without the involvement of mosquitoes is of interest, especially to rehabilitators who wonder if they must keep squirrels with fibromatosis isolated from healthy squirrels to prevent the latter from becoming infected. Additional routes of transmission could include direct animal-to-animal passage (such as through saliva, skin contact or respired air) and/or ectoparasites (i.e., externally living parasites such as fleas, lice and mites); multiple modes of transmission have been shown or are presumed to occur with some of the other poxviruses (Yuill, 1981; Fraser et al., 1991; see further discussion below). That non-mosquito transmission of this disease may occur is suggested by wildlife rehabilitators' reports that seemingly healthy squirrels contracted this disease after being caged with an infected squirrel, and by the occurrence of squirrels with fibromatosis when adult mosquitoes are scarce or absent (see further discussion below). For example, direct passage or ectoparasites may have been involved in fibroma virus transmission among caged groups of pre-release, rehabilitated fox and gray squirrels that were infested with mange mites or lice (Miller, 1992; 2000).

      To our knowledge, there are no published studies that specifically address the transmission of squirrel fibroma virus by direct passage or by ectoparasites. However, some information relevant to these potential modes of transmission is summarized below:

DIRECT PASSAGE OF THE VIRUS BETWEEN INFECTED & UNINFECTED SQUIRRELS (non-vectored transmission)

• Related viruses can be transmitted by direct passage
        Certain poxviruses have been shown or are presumed to be spread by direct passage (Yuill, 1981; Fraser et al., 1991). For example, myxoma virus of European wild rabbits (Oryctolagus cuniculus), although transmitted in nature primarily by insects (see 'Ectoparasite-vectored transmission' below), can also be passed between rabbits by the respiratory route when they come into close contact (Yuill, 1981).



• Intratracheal inoculation of fibroma virus did not produce external fibromas
        Intratracheal inoculation of squirrel fibroma virus suspension caused lung lesions or other pulmonary problems in some (4 out of 10) of the squirrels tested, but the formation of external fibromas in these animals was not reported (Kirschstein et al., 1958). This seems to be the only published study that provides any information which is relevant (even if only peripherally so) to the question of respiratory passage of this virus. However, the authors were not specifically addressing this issue but were instead interested in generating and studying lung lesions as seen in some squirrels with fibromatosis. Thus, uninfected squirrels were not exposed to respired air from infected ones. In addition, control animals (e.g., those given sterile physiological saline) were not included in the study, such that one cannot definitively determine which of the lung problems were caused by the 1-2 ml of fluid inoculated into the trachea and which by the virus itself (only two of the affected squirrels exhibited lung tissue changes reflective of the effects of the fibroma virus). Also, suckling squirrels, which appear to be more susceptible than adults (Kilham, 1955), were not tested.



• Fibroma virus was not transmitted from infected baby squirrels to their mothers
        The mothers of suckling squirrels with fibromatosis from experimental injections of virus did not contract the disease (Kilham, 1955). This finding suggests against transmission by the direct passage route (as well as against non-mosquito vectors if these squirrels had ectoparasites that moved from the babies to the mothers). However, it does not rule out either of these modes of transmission because too few animals were studied to reach firm conclusions; also, adult squirrels seem to be relatively resistant to fibromatosis, even when injected with the virus (Kilham, 1955).

ECTOPARASITE-VECTORED TRANSMISSION OF THE VIRUS

• Related viruses can be transmitted by more than one group of insects
        Myxoma virus is transmitted among O. cuniculus rabbits in nature primarily by mosquitoes and rabbit fleas (Ross, 1982), although experimental transmission also has occurred via rabbit lice, black flies (Simuliidae), ticks and mites (Yuill, 1981). Shope's fibroma virus of cottontails (Sylvilagus floridanus) has been transmitted in laboratory studies by five species of mosquitoes, three species of fleas* and four species of blood-sucking bugs (including bed bugs), although fleas were poor vectors and chigger mites did not transmit the virus (Kilham & Woke, 1953; Dalmat, 1959; Yuill, 1981).
  
  [*Note: This situation of "three species of fleas" as vectors of Shope's fibroma virus requires explanation. Kilham & Woke (1953) used groups of fleas from wild-caught cottontails in their transmission experiments. The fleas were later identified as three species (Cediopsylla simplex, Odontopsyllus multispinosus and Hoplopsyllus affinis [= H. glacialis affinis]), with the first two species predominating. Thus, which of the species vectored the virus cannot be determined. Also, of four cottontails used, only one acquired the virus. One of these flea species (H. affinis) has been reported from fox squirrels and one (C. simplex) from gray squirrels, along with seventeen other flea species, including the 'squirrel flea', Orchopeas howardi (Flyger & Gates, 1982).]



• Species related to squirrel ectoparasites can transmit pathogens to other animals
        Various species of fleas, lice, ticks and mites can vector pathogenic bacteria or viruses (Schmidt & Roberts, 1981; Yuill, 1981). For example, hog lice can spread swinepox among pigs (Fraser et al., 1991), mites can vector fowlpox virus of poultry (Schmidt & Roberts, 1981) and fleas, lice, ticks and mites can transmit myxoma virus among O. cuniculus rabbits (Yuill, 1981; Ross, 1982). However, other than the study of Kilham & Woke (1953) on fleas as vectors of Shope's fibroma virus of cottontails discussed previously, the species of ectoparasites that commonly occur on squirrels apparently have not been studied in regard to pathogen transmission . Although some mites transmit pathogens (see above), these species are classified in a different taxonomic category (i.e., a different 'suborder'), and thus may have different transmission capabilities, than the mange mites that occur on squirrels. In their extensive review of parasitic organisms, Schmidt & Roberts (1981) do not refer to any pathogens being transmitted by mange mites.



• Squirrels with fibromatosis may occur when adult mosquitoes are scarce or absent
        Given a relatively brief incubation period between injection of the virus and the appearance of external fibromas (7-14 days; Kilham, 1955), and the presumed likely alternatives of remission or death of infected animals within a month or two (Kilham, 1955; Miller, 1992; see Effects on the host animal [Link not yet available]), the occurrence of squirrels with fibromatosis during months when there are probably few or no active adult mosquitoes (see Geographic distribution & seasonality [Link not yet available]) suggests that this virus may be transmitted by other vectors or by direct passage between squirrels. There are, however, a number of unknowns that could influence this interpretation. For example, perhaps squirrels in nature can harbor the virus for several weeks before fibroma formation. Also, perhaps squirrels with fibromas can survive 3-4 months or more before undergoing remission or dying. For example, a captive-raised and subsequently released eastern gray squirrel was observed to develop wart-like lesions in the 'autumn' and eventually became moribund and died in early January with diagnosed fibromastosis (Novilla et al., 1981).

      Some of the items in the lists above provide at least suggestive support for the hypotheses that direct passage or ectoparasites of squirrels could spread this virus. However, definitive answers to these questions will only be obtained through research specifically designed to test these non-mosquito modes of transmission.

      Other questions about the transmission of squirrel fibromatosis also remain unanswered. For example:

• Even if they do not serve as vectors, can ectoparasites, especially at high numbers, stress squirrels to the point of making them more susceptible to the virus?

      Independent of their role as viral vectors, fleas, lice, mites and other ectoparasites (as well as mosquitoes and bot fly larvae) can variously trigger and/or suppress the different components of their host's immune system (Weisbroth et al., 1973; Barton et al., 1996; Wikel et al., 1996), but little information appears to be available on whether such effects may predispose an animal to viral infection. However, a number of environmental factors can influence an animal's immune system, thereby increasing its susceptibility to diseases (Thrusfield, 1995; Kelly et al., 1997). For example, poultry that are carriers of fowlpox may have the disease reactivated by the stress of molting or by other infections that suppress the immune system (Fraser et al., 1991). In that ectoparasites can produce a variety of deleterious effects, including dermatitis, excessive scratching, fur loss, reduced food intake, anemia and weight loss (Steelman, 1976; Rust & Dryden, 1997), their occurrence, especially at high densities, likely could impair their hosts' immune responses, making the parasitized animals more susceptible to pathogens (Wikel et al., 1996). For example, the saliva of certain ticks alters the immune responses of the host animal, which can facilitate the establishment of tick-borne pathogens (e.g., Wikel et al., 1996; Ferreira & Silva, 1998).


• Can infected squirrels develop immunity to this disease, and can mother squirrels provide immunity to their suckling offspring?

      In the only study of which we are aware that addresses the issue of postexposure immunity to squirrel fibromatosis, Kilham (1955) found that suckling squirrels (only 2 individuals were tested) did not develop new lesions at the site of a reinoculation occurring one week after their initial injection with fibroma virus. Kilham (1955) also demonstrated that blood serum of squirrels who's fibromas were regressing contained neutralizing antibodies lacking from uninfected squirrels. Immunity occurs with certain other pox diseases; for example, animals infected with sheeppox or swinepox virus develop longterm immunity (Fraser et al., 1991). Mother rabbits appear to transmit at least temporary immunity to myxoma virus to their offspring (Ross, 1982). In Kilham's (1955) study, several of the suckling squirrels kept with their mothers survived inoculation with fiboma virus, exhibiting only limited lesions and having their fibromas regress. These results are consistent with immunity transmitted from mother to infant; however, they are not definitive, as Kilham (1955) was not experimentally testing this aspect of immunity. Thus, baby squirrels raised on artificial formula rather than milk from their mother were not tested for comparison.


• Can squirrels that have recovered from fibromatosis become 'carriers' (i.e., remain infective)?

      For at least one poxvirus (fowlpox), infected individuals can become carriers (Fraser et al., 1991). However, whether a similar situation applies to squirrel fibromatosis is apparently unknown. Mosquitoes become infective when they feed on the fibromas (Kilham, 1955); that is, blood from a squirrel with fibromatosis obtained through the skin where fibromas are absent is probably minimally or non-infective. The influence of the age of fibromas on infectivity has apparently not been studied with squirrel fibroma virus. However, it is known for Shope's fibroma virus in cottontail rabbits that fibromas less than 7 days old are not infective (via mosquito transmission), but that once they become infective, they remain so until becoming so encrusted that mosquitoes cannot feed through them (Dalmat, 1959). Thus, once the fibroma lesions and nodules have regressed and healed, a squirrel that has recovered from fibromatosis presumably would not serve as a reservoir of the virus for mosquito-based transmission (nor probably for potential ectoparasite transmission). Of course, this hypothesis, and whether squirrels that have recovered from fibromatosis might remain contagious (direct passage route of transmission) need to be confirmed by direct research.


• Can other species of mosquitoes (in addition to the two species tested in a laboratory study) serve as vectors for squirrel fibroma virus?

      Certain other mosquito-vectored viruses have been identified from more than just one or two species of mosquitoes in nature (but note that just because an insect or other arthropod tests positive for a virus does not prove that it is involved in transmission). For example, considerable effort has been put into identifying potential vectors of West Nile virus (WNV; note that this is not a poxvirus but a flavivirus), especially because of the impact it can have on human health. Outside of the Americas, 43 species of mosquitoes have tested positive for this virus, with as many as 13 species in one country alone (Madagascar; Hubalek & Halouzka, 1999). During the 1999-2000 outbreak of WNV in the northeastern US, at least 7 species of mosquitoes have tested positive (CDC, 2000), but not, to our knowledge, Aedes aegypti or Anopheles quadrimaculatus, the two species Kilham (1955) showed capable of transmitting squirrel fibroma virus in a laboratory study. While it is apparently not known which mosquitoes feed on tree squirrels, given that a few squirrels in the northeastern US have tested positive for WNV (New York State Dept. of Health, 2000), it seems likely that in nature species of mosquitoes other than (or in addition to) the two studied by Kilham (1955) use squirrels to obtain a meal of blood and thus could vector squirrel fibroma virus.


• To what degree do the various species of tree squirrels differ in their susceptibility to fibromatosis?

      See Hosts for further discussion.

      Until more is known about the transmission of fibromatosis, indoor isolation of infected squirrels brought in for rehabilitation would seem to be a logical approach to help reduce the risk of transmission to uninfected squirrels by mosquitoes, by ectoparasites, if any of these are indeed vectors, and by direct passage, should this disease prove to be contagious. Within this context, Miller (1992) recommends that wildlife rehabilitators maintaining groups of squirrels in cages engage in "strict parasite control programs, closer observation of external parasites, and possibly the prophylactic use of ivermectin".

BOT FLY INFESTATION       In contrast to fibroma virus, bot fly larvae typically are not spread from infested to uninfested squirrels. Instead, squirrels are exposed when they contact eggs or newly hatched (= infective-stage) larvae on foliage, branches or other objects in their habitat (Fig. 2). This occurs because, as far as is known (but note that records exist for only a few species), the broad-bodied, black and pale yellow female tree squirrel bot flies (Fig. 3), as well as females of other rodent- and lagomorph-infesting bot flies, lay their eggs on substrates in the habitat rather than directly on their hosts (Fig. 4). This 'off host' egg-laying behavior contrasts with that of certain other bot flies, such as the horse stomach bot fly, and with other parasitic flies, such as the maggot-producing blow flies, which lay their eggs (or in some species, the female fly deposits maggots) directly on the host (Catts, 1982; Wall & Shearer, 1997).

Fig. 2: Eastern gray squirrel moving along a branch may become infested with tiny bot fly larvae	Fig. 3: Adult tree squirrel bot fly (head to left)*	Fig. 4: Bot fly eggs laid on a twig*
	(*Note that about 1/3 of the length of this fly's dark wings have been broken off, due to its flying around in a jar prior to the photo)	(*Note that although these look similar to the eggs of the tree squirrel bot fly, they are from a different species, Cuterebra americana, which parasitizes eastern wood rats)

      Infective-stage larvae that get on a squirrel and enter one of the animal's body orifices or a wound begin their approximately week-long journey through the host's body, eventually settling under its hide. Here the larvae use their pointed mouth hooks to cut through the host's hide to create a warble pore, and their presence produces the characteristic warbles, where they typically remain until completing their development. Individual squirrels apparently can become infested on more than one occasion (perhaps over a period of a week or more), such that they contain various-sized larvae at different stages of development, manifesting as a broad range of warble sizes in heavily infested squirrels (see Fig. 2 in External appearance). In rare cases, suckling squirrels that have never left their nest are seen with warbles (Fig. 5). How they become infested is unknown, but this might occur when infective-stage larvae picked up by a mother squirrel while she is out foraging transfer to her offspring when she returns to the nest (FIg. 6). Another possibility is that infective-stage larvae from eggs laid on the leaves and twigs comprising the nest enter it and locate the babies.

Fig. 5: Three- to four-week-old suckling eastern gray squirrel with a bot fly warble on its hip, infested prior to leaving its nest	Fig. 6: After foraging, a mother squirrel may inadvertently bring back to its nest infective-stage larvae that then infest her babies

      Occasionally, atypical hosts such as raccoons, cats, dogs and humans also become infested by representatives of this group of parasitic flies (Sabrosky, 1986), with exposure presumably occurring when they move through vegetation, brush against twigs or otherwise contact infective-stage larvae. Which species of rodent/lagomorph bot flies infest pets and people has seldom been determined because the immature larvae are often removed from the host, and these are difficult to identify to species. We are aware of only two records of a tree squirrel bot fly larva identified from unusual hosts (a dog and a cat; French, 1893; Sabrosky, 1986). Mice, rat, and rabbit-infesting bot flies have been implicated (or occasionally identified) in cases involving pets and humans (e.g., Hatziolos, 1966; Salomon et al., 1970; Shorter et al., 1997).

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     Frank Slansky & Lou Rea Kenyon || fslansky@ufl.edu

     Version 1.1 (updated July 26, 2001)