Clarification on drugs used to treat leishmaniasis

In the recent JAVMA article “Guidelines for treatment of leishmaniasis in dogs,”¹ there were lists of several drugs to treat this disease, including allopurinol, aminosidine, metronidazole, and pentamidine.

The authors included the comment for each of these drugs that they are “FDA approved for use in dogs.” They are not. This is an important error to correct for readers. The FDA process of approval has several requirements, including target animal safety and efficacy. The authors' statements give the false impression that these drugs are approved for use in dogs, which implies that such proof is available.

Whether particular drugs have been approved by the FDA for use in dogs can easily be checked. Simply go to the Animal Drugs @ FDA website² and enter the drug name in the search window.

Mark G. Papich, dvm, ms

Department of Molecular Biomedical Sciences

College of Veterinary Medicine

North Carolina State University

Raleigh, NC

Questions study on the use of pheromones in dogs and cats

I write concerning the recent article “Systematic review of the use of pheromones for treatment of undesirable behavior in cats and dogs.”¹ As a representative of the company that develops, produces, and markets the products referred to, I believe it is important to comment on what I believe to be a seriously flawed report.

First, I appreciate the authors' initiative. To my knowledge, this is the first time such a review has been attempted in the pet behavior field. I assume that this is due to the lack of published research on other products used in that field. Unfortunately, I believe that the published work falls short of the scientific standards of a systematic review and that it is not authoritative, as it should be, and is misleading. I believe that both the content and the tone of the article are questionable.

Concerning content, I would suggest that this review does not comply with the recommended guidelines for conducting a systematic review. Unfortunately, the authors do not appear to have taken the necessary care when evaluating the published reports. For example (space does not permit a longer list of errors), in Table 1, they repeat an error made in the report² concerning the effect of feline facial pheromone on spraying. In that study, week five was the fourth week of treatment because week one was the baseline period, and at this time, 15 of 17 cats had shown partial clinical remission, not the 14 of 19 cats the authors report. The authors have erroneously used data from week four, which is the third week of treatment. Such poor review of the data is repeated elsewhere, and it is concerning that if the reports were reviewed independently, as claimed, different authors made the same error.

I also question the scientific appropriateness of including studies whose objectives are not in accordance with the title of the paper. Neither idiopathic cystitis nor IV catheterization can be considered undesirable behaviors.

Concerning tone, I believe that the authors were consistently negative rather than impartial. Systematic review guidelines emphasize the importance of respect for selected publications. All the trials quoted have been published in reputable, peer-reviewed, scientific journals, including JAVMA, and although not perfect, they can inform an evaluation of efficacy. This review fails to highlight the lack of good evidence, according to the authors own standards, for the management of most of the conditions listed and thus ignores the inevitable conclusion that some evidence is better than none. Thus, as written, the report offers no constructive advice for readers.

Finally, as the manufacturer of the products, CEVA cannot accept that the authors speculate on the mode of action on the basis of erroneous information. They suggest that the efficacy of feline facial pheromone–based products is solely linked to the presence of Valeriana officinalis extract. However, Feliway diffuser, the most widely used form in the field, does not contain valeriana.

Unfortunately, space does not permit a more comprehensive rebuttal of this publication.

Alexandra Beck, DVM

Behavior Technical Manager

CEVA Santé Animale

Libourne, France

Additional comments on the cause of spinal cord compression in a dog

I read with interest the authors' response¹ to a critique² of the interpretation in their “What Is Your Diagnosis?” report³ of an eight-year-old Japanese Chin with a history of intermittent neck pain and acute-onset ataxia. I agree that the anatomy and development of the occipitoatlantoaxial region in dogs is complex; however, it is well documented and abundantly illustrated in the standard canine anatomy text⁴ and research papers.^5–7 I reject the authors' hypothesis of the development of the abnormalities in this dog for four reasons. First, dogs of toy and miniature breeds often have poorly developed occipital condyles and large vertebral and lateral vertebral foramina.⁶ Second, in mammals, the body of C2 develops from three separate embryologic centra and a distinct bony intercentrum 2 (between centrum 1 and centrum 2) and is capped caudally by the first epiphysis in the vertebral column.^4,5 The absence of the dens in this dog was more likely an acquired lesion that resulted from an earlier post-natal vascular insult, rather than the result of a congenital absence of an ossification center.⁵ Third, the first intervertebral disk in dogs (indeed, in mammals generally) is that between C2 and C3; there is no evidence (radiographic or histologic) for an intervertebral disk within the body of C2 in dogs whether normal or abnormal.^4,5,7 Fourth, the authors provide conflicting interpretations of their radiographs. For example, the statements that “…the body [intercentrum 1] of the atlas is shortened”³ and that there was “…a failure of centrum one to separate from intercentrum one, resulting in an enlarged ventral arch [body] of C1 and an absence of a dens on C2…”¹ are inconsistent statements. The posited enlargement of the body of C1 is not apparent in the radiographs. Further, a substantial cranial portion of the body of C2 is clearly present; this part of the body of C2 develops from the caudal part of centrum 1 plus intercentrum 2. Thus, centrum 1 cannot have failed to separate as suggested. Moreover, the bony lesions in this dog are not, as the authors state, “…consistent with occipitoatlantoaxial malformation….” Such malformations in dogs (and other mammals) have a distinctive suite of morphological features, including atlanto-occipital fusion, malformation of C1 with reduced transverse processes, and an atlantoaxial joint resembling the species-specific atlanto-occipital joint.⁷ None of these features was present in this dog.

I do not question that the spinal cord was compressed at the atlantoaxial level, although the authors present no convincing evidence regarding the etiology of this compression. Conjecture that “[a] herniated disk at the intervertebral disk space of C1-2…”³ caused the compression is not tenable for the anatomic and developmental reasons stated. A more likely explanation has been provided.²

In summary, I concur with the earlier critique that this report “…better demonstrates the importance of knowing the anatomy of the vertebral column in dogs.”²

Alastair Watson, BVSc, MAgrSc, PhD

Department of Physiological Sciences

Center for Veterinary Health Sciences

Oklahoma State University

Stillwater, Okla

Potential consequences of inhaling intranasal and aerosolized vaccines

I would like veterinarians to ponder the idea of vaccinating themselves, their staff members, and their clients against feline herpes virus, Bordatella spp, parainfluenza virus, and FeLV.

The reason I want veterinarians to ponder this idea is because that is exactly what we are doing when administering intranasal or aerosolized vaccines.

We would never inject ourselves with vaccines intended for use in animals, so why do we think it is safe to inhale them? Have the vaccine companies proven that the material produced when a dog or cat sneezes during vaccination with an intranasal vaccine has no biological consequences when inhaled by people? Is it safe for a pregnant staff member, a client receiving chemotherapy, a person with HIV, or a child in the room with the pet? How about when the animal goes home? Are veterinarians aware that Bordatella brochseptica and parainfluenza virus are potentially zoonotic?

The aerosolized FeLV vaccine is administered in a way that some of the vaccine is dispersed into the air. Holding the injection device against the animal's fur does not provide an airtight seal.

Everyone is aware that accidental injection of the intranasal Bordatella vaccine in a dog can have severe consequences. Why would we assume that accidental inhalation of the vaccine will not have any consequences? I consider unintentional but consistent inhalation of animal vaccines to be potentially unsafe and hope the FDA gives this technique a much more thorough evaluation.

I would like to remind readers that even if a titer does not develop in an exposed person, this does not mean the vaccine did not have any effect on cells in the body. In addition, when a company states that a vaccine virus does not infect a human cell culture line, this does not mean that all human cells will not be infected. Cell culture lines are specific and do not represent all human cells.

Scott R. Palmer, VMD

Santa Barbara, Calif

Another perspective on feral cat control

We disagree with Dr. Ackerman's opinion¹ that the human health risks associated with feral cats is low, and we know of no peer-reviewed research supporting this statement. Documented exposure to rabid feral cats is relatively rare, compared with exposure to rabid wildlife, but more common than exposure to other domestic species in most states. In New York state, from 1993 to 2002, cats accounted for 2.7% of rabid terrestrial animals but accounted for a third of human exposure incidents (4,266) and postexposure prophylaxis (PEP) treatments (5,777).² At trapneuter-release (TNR) feeding sites, rabies-susceptible wildlife compete for food with cats, and those cats subsequently have regular close association with humans, resulting in potential exposure. This same pattern—high proportions of PEP treatments associated with stray cat contacts—occurs nationwide, and PEP is expensive, with costs largely borne by the public. The rabies infection rate in cats is stable, not declining, at about 4% from 2004 to 2008 inclusive.³ To reduce the risk of rabies, the CDC recommends that stray cats be removed from the community.³

Some TNR programs vaccinate cats for rabies, but many do not. The largest TNR program ever conducted in California resulted in the release of 90,000 feral cats not vaccinated for rabies.⁴ Importantly, to maintain rabies-free status from a veterinary public health standpoint, feral cats would need to receive appropriate rabies booster vaccinations and following a bite from an animal of unknown rabies status (eg, a wild carnivore or bat), be revaccinated immediately and observed for 45 days.³ This is impossible with feral cats, so trap-neutervaccinate-release has little potential to reduce PEP and its associated costs. Hopefully, public health epidemiologists are not suggesting one vaccination and PEP standard for owned cats and another for feral cats.

Dr. Ackerman states that trapping and removing cats has not been found to be effective because as long as the environment supports a certain population size, sexually intact females will continue to breed and other animals will move in. The environment does not support feral cat colonies. Continual provision of food does. Removing cats from the environment reduces overall numbers, something we all, hopefully, are trying to achieve. The failure to observe this reduction at the colony level may be a matter of redistribution, reproduction, or continued abandonment. Even TNR advocates recognize it “enables” abandonment. The largest followup study,⁴ one published by TNR advocates, shows that large-scale TNR does not result in long-term reduction in the number of feral cats. Removal takes feral cats out of environments where they get killed by cars, dogs, wildlife, disease, and extremes of weather and where they kill and maim many millions of wildlife.⁵ In contrast, TNR and trap-neuter-vaccinate-release do not.

Over the past three years, we have viewed with alarm a pattern of inviting advocates of TNR to national public health meetings and a steady refusal to include other perspectives. Public health decisions are too important to allow empathy and philosophical bias to override science. We need comprehensive, community-based programs that protect feral cats, wildlife, and their ecosystems as well as public health. Nothing less will do.

David A. Jessup, DVM, MPVM, DACZM

California Department of Fish and Game

Santa Cruz, Calif

Elizabeth Stone DVM, MS

Director, Center for Wildlife Health Research

Pownal, Me

Requests more information on hyperphosphatasemia study

Regarding the report “Hyperphosphatasemia and concurrent adrenal gland dysfunction in apparently healthy Scottish Terriers,”¹ I would first like to thank the authors for this informative report on this very common condition. The authors state that “No association was detected between sex and ALP [alkaline phosphatase] activity.” Could the authors comment further whether any association was found between neuter status and ALP activity?

Shelley R. Epstein, VMD

Wilmington Animal Hospital

Wilmington, Del

The authors respond:

The authors thank Dr. Epstein for her question regarding whether there was any association between neuter or spay status and serum alkaline phosphatase (ALP) activity in our study “Hyperphosphatasemia and concurrent adrenal gland dysfunction in apparently healthy Scottish Terriers.”¹ As we mentioned in the original report, there was insufficient evidence (χ² test; P = 0.163) to reject the null hypothesis that ALP activity status (high vs normal) was the same between males and females in the study. Although not reported, we did investigate the very question posed by Dr. Epstein. The distribution of sex and neuter status of the study animals was mentioned as a footnote in Table 1.

Again, there was insufficient evidence (χ² test; P = 0.076) to reject the null hypothesis that ALP activity status (high vs normal) was the same between sexually intact males, sexually intact females, spayed females, and castrated males in the study. However, this conclusion is suspect and was not reported owing to the limited number of dogs in several of these subgroups. For this reason, these subgroups were assimilated into the larger male and female groups, creating categories of adequate size for statistically valid assessment. Dr. Epstein's question remains of interest despite our inability to fully answer her question. Simple visual inspection of the sex and neuter status distribution suggests spay status was not likely related to ALP status, but the possibility of a relationship with neuter status alone is less clear. Hopefully, a future, larger, balanced study will be able to answer this interesting question.

Kurt L. Zimmerman, DVM, Phd, dacvp

David L. Panciera, DVM, MS, DACVIM

Virginia-Maryland Regional College of Veterinary Medicine

Virginia Tech

Blacksburg, Va