Serologic response in eight alpacas vaccinated by extralabel use of a large animal rabies vaccine during a public health response to a rabid alpaca in South Carolina

Ryan M. Wallace Poxvirus and Rabies Branch, CDC, Atlanta, GA 30307.

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Michael Niezgoda Poxvirus and Rabies Branch, CDC, Atlanta, GA 30307.

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Emily A. Waggoner Large Animal Veterinary Services, 1602 Levis Smith Rd, Pendleton, SC 29670.

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Jesse Dean Blanton Poxvirus and Rabies Branch, CDC, Atlanta, GA 30307.

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Rachel A. Radcliffe South Carolina Department of Health and Environmental Control, 2600 Bull St, Columbia, SC 29201.

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Abstract

CASE DESCRIPTION A female alpaca, kept at pasture with 12 other female alpacas, 2 crias, and 5 goats, was evaluated because of clinical signs of aggression.

CLINICAL FINDINGS The clinical signs of aggression progressed to include biting at other animals as well as disorientation. Three days later, the alpaca was euthanized because of suspicion of rabies virus infection.

TREATMENT AND OUTCOME No physical injuries were found at necropsy. Brain tissue specimens were confirmed positive for rabies on the basis of direct fluorescent antibody test results. Molecular typing identified the rabies virus variant as one that is enzootic in raccoons. The farm was placed under quarantine, restricting movement of animals on and off the property for 6 months. To prevent further rabies cases, 14 alpacas (12 adults and 2 crias) were vaccinated by extralabel use of a large animal rabies vaccine. Of the 14 vaccinated alpacas, 8 had paired serum samples obtained immediately before and 21 days after vaccination; all 8 alpacas had adequate serum antirabies antibody production in response to rabies vaccination. As a result of an adequate serologic response, the quarantine was reduced to 3 months. In the year after the index rabies case, no other animals on the farm developed rabies.

CLINICAL RELEVANCE Extralabel use of rabies vaccines in camelids was used in the face of a public health investigation. This report provides an example of handling of a rabies case for future public health investigations, which will undoubtedly need to develop ad-hoc rabies vaccination recommendations on the basis of the unique characteristics of the event.

Abstract

CASE DESCRIPTION A female alpaca, kept at pasture with 12 other female alpacas, 2 crias, and 5 goats, was evaluated because of clinical signs of aggression.

CLINICAL FINDINGS The clinical signs of aggression progressed to include biting at other animals as well as disorientation. Three days later, the alpaca was euthanized because of suspicion of rabies virus infection.

TREATMENT AND OUTCOME No physical injuries were found at necropsy. Brain tissue specimens were confirmed positive for rabies on the basis of direct fluorescent antibody test results. Molecular typing identified the rabies virus variant as one that is enzootic in raccoons. The farm was placed under quarantine, restricting movement of animals on and off the property for 6 months. To prevent further rabies cases, 14 alpacas (12 adults and 2 crias) were vaccinated by extralabel use of a large animal rabies vaccine. Of the 14 vaccinated alpacas, 8 had paired serum samples obtained immediately before and 21 days after vaccination; all 8 alpacas had adequate serum antirabies antibody production in response to rabies vaccination. As a result of an adequate serologic response, the quarantine was reduced to 3 months. In the year after the index rabies case, no other animals on the farm developed rabies.

CLINICAL RELEVANCE Extralabel use of rabies vaccines in camelids was used in the face of a public health investigation. This report provides an example of handling of a rabies case for future public health investigations, which will undoubtedly need to develop ad-hoc rabies vaccination recommendations on the basis of the unique characteristics of the event.

On December 21, 2014, a female alpaca from a farm in South Carolina developed clinical signs consisting of aggression, biting at other animals, and disorientation. The alpaca was treated with mineral oil administered via a nasogastric tube and anti-inflammatory medication, but clinical signs progressed and on December 24, the alpaca was euthanized by IV injection of sodium pentobarbital solution because of suspicion of rabies virus infection. On December 26, brain tissue specimens from the alpaca were confirmed positive for rabies on the basis of direct fluorescent antibody test results. Molecular typing identified the variant as one that is enzootic in raccoons throughout the eastern United States. At the time of euthanasia, no physical injuries were found on the alpaca. Neither the rabid alpaca, nor other alpacas on the farm, had been previously vaccinated with a rabies vaccine. Rabies virus shedding has been studied in dogs and cats and has been shown to occur only within 10 days preceding the onset of clinical signs.1 Viral shedding studies have not been conducted in other animals, and a more conservative 14-day shedding period is typically assumed out of an abundance of public health caution. Therefore, the rabid alpaca was considered to have been infectious from December 7 through December 26.1

The farm of the rabid alpaca had allowed the public to tour the grounds while having direct contact with the animals. Fortunately, no public events were held at the farm during the rabid alpaca's infectious period. The South Carolina Department of Health and Environmental Control assessed 4 people for contact with saliva or nervous tissue from the rabid alpaca as follows: 2 farm owners, a family member of the farm owners, and a veterinarian. These individuals reported extensive handling of the rabid alpaca during the infectious period. The 2 farm owners had direct contact with saliva while assessing the alpaca for possible intraluminal esophageal obstruction (ie, choking) and while attempting syringe feedings. The owners could not rule out saliva contact to their mucous membranes or fresh wounds and received rabies postexposure prophylaxis.2 The veterinarian who provided medical care to the alpaca wore gloves and eye protection and was able to rule out contact with saliva or nervous tissue; rabies postexposure prophylaxis was not recommended. The family member had no direct contact with saliva or nervous tissue from the rabid alpaca; rabies postexposure prophylaxis was not recommended.

The farm consisted of 13 female alpacas (including the rabid alpaca), 2 crias, and 5 goats located on pasture A and 8 male alpacas and 2 horses confined to pasture B. The source of the rabid alpaca's infection was unknown and exposure of other animals on the farm to rabid animals could not be ruled out. Therefore, South Carolina Department of Health and Environmental Control, with consultation from the CDC, immediately recommended that all public events on the farm be postponed for a 6-month period or until further public health investigations could be completed. Pastures A and B were separated by a hay field; therefore, concern about secondary exposure to the rabid alpaca were relegated to the maternal herd and other animals housed on pasture A. Farm owners observed the rabid alpaca bite another alpaca on the hind limb 2 days after developing clinical signs. No other bite exposures to the rabid alpaca were observed, but given the communal housing of animals in pasture A, additional bite and non-bite exposure to the rabid alpaca could not be ruled out. Consequently, all animals in pasture A were placed under quarantine, restricting movement on and off the pasture for a 6-month period.

As a precaution to prevent further rabies cases on the farm, on January 9, 2015, the surviving 12 adult alpacas and 2 crias from pasture A were vaccinated, in an extralabel manner, with a large animal rabies vaccine.a Five goats housed on pasture A were also vaccinated, according to manufacturer's instructions.a Nine alpacas had blood drawn just before vaccination. Of these 9 alpacas, 8 also had blood drawn 21 days after vaccination on January 30 to assess the immune response to extralabel use of rabies vaccine. Serum samples were analyzed for antirabies antibody production by means of a rapid fluorescent focus inhibition test at the rabies laboratory of the CDC.b None of the 9 alpacas had detectable serum antirabies antibodies on the day of vaccination. All 8 alpacas at 21 days after vaccination had detectable serum antirabies antibodies; serum antirabies antibody titers ranged from 0.1 to 10.4 U/mL (mean titer, 3.1 U/mL). Two of the 8 alpacas had low yet still detectable serum antirabies antibody titers (0.23 U/mL and 0.1 U/mL). All 8 alpacas had a complete rabies virus neutralizing antibody titer at a 1:5 dilution, an indication that an adequate immune response has occurred per the ACIP recommendations for serologic testing in humans.3

As a result of confirmation of adequate rabies vaccination by serologic testing and finding no other evidence of increased rabies activity in the area surrounding the farm, the quarantine period for herd A and the public events ban for the farm was reduced to 3 months. The farm owners were counseled to remain vigilant for ill animals on the farm for the original 6-month period. On March 26, 2015, 3 months from when the rabid alpaca was euthanized and with no further rabies activity found, the quarantine was lifted. During the 12 months following the index rabies case, no further rabies cases were identified on the farm.

Discussion

Rabies is caused by a neurotrophic virus capable of infecting all mammals, including humans, with a case fatality rate approaching 99.9%. Worldwide, an estimated 59,000 people die of rabies each year, primarily from the bite of an infected dog.4 In regions where the canine rabies virus variant has been eliminated, wildlife rabies reservoir species have shown to play an increasing role in human and domestic animal exposures. In the United States, there are 5 rabies virus variants that circulate in 8 wildlife animal species and > 13 variants associated with bats. Each year, approximately 500 domesticated animals become infected through cross-species interactions with wildlife reservoirs, yet relatively few of these domestic cases have been reported for camelids.5–8 The raccoon rabies virus variant was detected in brain tissue specimens from the alpaca of the present report; this is the terrestrial variant enzootic to South Carolina.

Vaccination of domesticated animals is the primary intervention for rabies control programs. In the United States, there are at least 22 licensed rabies vaccines approved for use in 6 domestic and 2 wildlife animal species (ie, dogs, cats, ferrets, sheep, horses, and cattle, and coyotes and raccoons, respectively).9 Extralabel use of rabies vaccine is recommended by the NASPHV for livestock that have frequent contact with humans, such as animals in a petting zoo or animals that participate in exhibitions.9 However, because of a dearth of published data on the effectiveness of extralabel use of rabies vaccines, these animals are typically not considered vaccinated for the purposes of a public health investigation. For example, if an alpaca vaccinated with rabies vaccine were to bite a person, the vaccination status of that alpaca would not be considered valid by public health professionals and most likely the animal would be euthanized and tested. Furthermore, observation periods for suspected rabid animals are only valid for dogs, cats, and ferrets.9 For species in which there are no approved rabies vaccines or approved periods of observation after human exposure to a potentially rabid animal, there are currently few alternatives to euthanasia and testing.

Current NASPHV9 recommendations for the public health response for livestock and herd animals in the face of exposure to rabid animals are limited. Section 5.4.b.1 of these recommendations states that exposed, unvaccinated animals should be euthanized immediately, and those that are not exposed should be confined and observed on a case-by-case basis for 6 months.9 Section 5.4.b.4 states that herbivore-to-herbivore transmission of rabies is uncommon and restricting the herd if a single animal has been infected with rabies is usually not necessary.9 These recommendations appear to be in contradiction to each other but likely refer to the differences in perceived risk of an exposure to a rabid terrestrial carnivore (highlighted by section 5.4.b.1), compared with the lower risk of herbivore exposures (ie, section 5.4.b.4). Rabies virus transmission in herbivores is rarely documented in published literature, and this may be a result of observations that cattle (the most common rabid herbivore) more frequently have signs consistent with the paralytic form of rabies and that most herbivores lack canine teeth, which may decrease the likelihood of traumatic bite wounds.7 However, male (and the occasional female) camelids have 6 canine teeth that are used to severely wound opponents.10 Furthermore, while limited, published cases of rabid camelids commonly describe aggression as a clinical feature of disease, as was observed in the alpaca of the present report, and camelids are known to spit when anxious. Both of these behavioral traits pose the potential to facilitate increased risk of transmission of rabies virus, compared with noncamelid herbivores.5,6 Because of this unique dental anatomy and behavior of camelids, these herbivores may be more biologically primed for transmission of rabies virus. However, rabies infections in camelids are rare, and camelid-to-camelid transmission of rabies virus has not yet been documented.

In the scenario described in the present report, a herd of unvaccinated camelids were exposed to both the rabid alpaca as well as the rabid animal that caused this infection. This highlights the common scenario in which animal owners and veterinarians do not know when and how herd animals are exposed to rabid animals and the challenges public health authorities face in developing suitable recommendations after potential exposure to a rabid animal. The lack of clarity in regards to public health practices often result in these situations being addressed on a case-by-case basis.

Both state and federal public health authorities had to consider the aggressive nature of the rabid alpaca, the unique dentition of camelids (compared with that of other herbivores), that the surviving alpaca had numerous opportunities for other unobserved exposures, and that the farm was open to the public. Therefore, more emphasis was placed on NASPHV section 5.4.b.1 and a conservative recommendation was made to place herd A under quarantine. However, per section 5.4.b.4, this action may have been overly conservative. As a compromise, it was agreed that if the animals from pasture A were vaccinated by extralabel use of rabies vaccine and had evidence of adequate serum antirabies antibody production, that the quarantine period could be reduced to 3 months.

The 8 alpacas that underwent serologic testing before and after rabies vaccination all had an antirabies antibody response. However, there is lack of clarity as to what an adequate immune response entails for animals. The World Health Organization requires a serum antirabies antibody titer of ≥ 0.5 U/mL as evidence of adequate vaccination in dogs and cats for the purpose of international travel. The ACIP uses a criterion of a serum antirabies antibody titer of ≥ 0.11 IU/mL (equivalent to an antibody titer of 1:5) for proof of adequate serologic conversion in humans.3 Of note, NASPHV compendium recommendations do not specify which of these values should be used to assess an animal's antibody response to rabies vaccination. Per the ACIP, adequate vaccination was achieved in all 8 alpacas tested; however, only 6 of 8 alpacas met WHO criteria. State and federal authorities decided to use ACIP recommendations for this specific situation and agreed that the criteria to lift the quarantine ban had been met and it was subsequently lifted. It should also be noted that there is a range of time in which the peak immune response to a vaccine may be reached; serologic testing on only day 21 after vaccination may not reflect the peak serum antirabies antibody titers achieved by these alpacas.

This report provides the first published evidence for extralabel use of rabies vaccine in camelids in the face of a public health investigation. All alpacas that were serologically tested had evidence of antirabies antibody production following vaccination; however, there are limitations to drawing conclusions from a field trial conducted during a public health investigation. Serologic testing was performed on a limited sample size, the trial included only female alpacas, and the past and present health conditions of the affected alpaca were not considered in the analysis. Furthermore, there are rare instances of documented herbivore-to-herbivore transmission of rabies virus, so it is difficult to say whether the extralabel use of rabies vaccine prevented further rabies cases in the herd of the present report or whether no further cases would have occurred without vaccination. Lastly, only antirabies antibody production was measured in this report. It is impossible to determine whether the vaccination would have resulted in protection against developing rabies in the face of a rabies challenge. These studies would need to be conducted in controlled settings, not during a public health investigation. This report highlights several limitations in current rabies control recommendations in atypically affected species but also provides some direction for future public health investigations, which will undoubtedly need to develop ad hoc recommendations on the basis of the unique characteristics of the event. Although limited in scope, this report does provide evidence that a shortened quarantine period, under certain conditions, may be appropriate.

Acknowledgments

The views expressed here are those of the authors and do not necessarily reflect the views of the federal government.

The authors thank Travis L. Shealy for technical assistance.

ABBREVIATIONS

ACIP

Advisory Counsel for Immunization Practices

NASPHV

National Association of State Public Health Veterinarians

Footnotes

a.

IMRAB Large Animal, Merial Ltd, Duluth, Ga. 6.

b.

Rabies Laboratory, CDC, Atlanta, Ga.

References

  • 1. Tepsumethanon V, Lumlertdacha B, Mitmoonpitak C, et al. 8. Survival of naturally infected rabid dogs and cats. Clin Infect Dis 2004;39:278280.

  • 2. Manning SE, Rupprecht CE, Fishbein D, et al. Human rabies 9. prevention–United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2008;57:128.

    • Search Google Scholar
    • Export Citation
  • 3. Rupprecht CE, Briggs D, Brown CM, et al. Use of a reduced 10. (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the advisory committee on immunization practices. MMWR Recomm Rep 2010;59:19.

    • Search Google Scholar
    • Export Citation
  • 4. Hampson K, Coudeville L, Lembo T, et al. Estimating the global burden of endemic canine rabies. PLoS Negl Trop Dis 2015;9:e0003709.

  • 5. Whitehead CE, Bedenice D. Neurologic diseases in llamas and alpacas. Vet Clin North Am Food Anim Pract 2009;25:385405.

  • 6. CDC. Rabies in a llama–Oklahoma. MMWR Morb Mortal Wkly Rep 1990;39:203204.

  • 7. Monroe BP, Yager P, Blanton J, et al. Rabies surveillance in the United States during 2014. J Am Vet Med Assoc 2016;248:777788.

  • 8. Blanton JD, Dyer J, McBrayer J, et al. Rabies surveillance in the United States during 2011. J Am Vet Med Assoc 2012;241:712722.

  • 9. National Association of State Public Health Veterinarians, Compendium of Animal Rabies Prevention and Committee, Brown CM, et al. Compendium of Animal Rabies Prevention and Control, 2016. J Am Vet Med Assoc 2016;248:505517.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Cebra C, Anderson DE, Tibary A, et al. Llama and alpaca care: medicine, surgery, reproduction, nutrition, and herd health. St Louis, Mo: Elsevier, 2014; 38, 477.

    • Search Google Scholar
    • Export Citation
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