Injection sarcomas in cats (Proceedings)

1) Adjuvants and Vaccine Associated Sarcomas

a) Incidence of VAS

i) VIN, 12/19/06: 22,000 per year

(1) Source: Are We Vaccinating Too Much; JAVMA, Aug 15, 1995

(a) Dennis Macy: "I estimate there are about 22,000 cases of vaccine associated tumors per year."

(b) No reference is given for this statement and no references appear at the end of the chapter for any statements made in the article.

ii) ... a 0.5-1.0 ratio per 10,000 cats adds up to 1000-2000 affected cats per year in the US.

(1) Kirpensteijn J. Feline injection site-associated sarcoma: Is it a reason to critically evaluate our vaccination policies? Vet Microbio. 2006;117:59-65.

iii) Norsworthy's calculation

(1) 1:10,000: incidence of VAS

(2) 90.5 M "owned cats" per USA Today, Feb. 18, 2007

(3) 25% of these are vaccinated per year

(4) Total = 2263 VAS per year in the US.

b) JAVMA, Jan. 1, 2007: Response of Feral Cats at the Time of Neutering

i) One dose of MLV FVRCP had NO increase in protective titer over 10 weeks (28% to 28%)

ii) One dose of killed adjuvanted FVRCP had an increase from 16% to 81% protective titer over 10 weeks.

iii) Conclusion: Adjuvants GREATLY increase efficacy.

c) Claim of no inflammation with a needleless injection system:

i) Supplement to NAVC Clinician's Brief by Merial

ii) "Transdermal Technology: Developed by Merial for vaccine administration through the skin, VETJET™ transdermal vaccination technology disperses the antigen into the dermis, subcutis, and muscle, optimizing exposure to antigen processing cells and avoiding inflammation."

d) Role of inflammation on the cause of VAS

i) Vaccine Sarcoma Task Force's Final Report, JAVMA June 1, 2005

(1) Question: Building on that point, do we have evidence that injectable products that induce inflammation are more likely to be associated with sarcoma development?

(a) Dr. McClure: It is very important to note the statement, "inflammation secondary to injection is a necessary precedent to sarcoma formation," is a hypothesis.

(b) Dr. Kitchell: But, it is a big leap of faith to say that it is solely the inflammatory reaction that induces a sarcoma. That leap has not been filled in with any kind of concrete structure. It takes the right kind of triggering event in the right individual cat to lead to neoplastic transformation.

ii) Role of genetics in VAS

(1) Vaccine Sarcoma Task Force's Final Report, JAVMA June 1, 2005

(a) Question: Is there evidence to support the contention that the genetics of cats plays a role in the development of vaccine-associated sarcomas?

(i) Dr. Dennis Macy: In my personal experience, I know of a situation in which cats from the same litter developed sarcomas at injection sites, even though they went to separate veterinarians and received various substances.

(ii) Dr. Glickman: A difference in the incidence of VAS in different communities may suggest a genetic predisposition.

(2) Dr. Richard Ford, in Clinician's Brief, March 2006: "An allele has recently been identified in cats predisposed to developing VAS." Referring to Amer J Vet Res, Oct. 2006: Somatic alterations of the p53 tumor suppressor gene in vaccine-associated feline sarcomas.

e) Incidence of VAS

i) Vaccine Sarcoma Task Force's Final Report, JAVMA June 1, 2005

(1) Dr. Ron Schultz: It may be sufficient for practitioners to inform clients that there may be a potential problem, but the problem is rare.

f) Will using non-adjuvanted vaccines reduce the incidence of VAS?

i) VAFSTF (JAVMA, 6/1/05): Can we say that the more inflammation a vaccine induces, the more likely a sarcoma will form?

(1) Dr. Hendrick: "I don't think we can say the more inflammation a vaccine induces, the more likely a sarcoma will form."

ii) JAVMA, Nov. 1, 2003

(1) Phil Cass, Multicenter case-control study of risk factors associated with development of vaccine-associated sarcomas in cats: Based on a study of 33,000 cats he concluded that there is no difference in the incidence of vaccine-associated sarcomas with adjuvanted and non-adjuvanted vaccines.

iii) Veterinary Record, June 2, 2007

(1) "The VMD received 39 reports of injection-site sarcomas in cats, an increase of five reports compared to 2005. Twenty-three reports were associated with live vaccines, six with inactivated vaccines, nine with mixed vaccines and one with an ectoparasiticide."

(a) Note: There was in increase of 15% of reported sarcomas.

(b) There was also an increase of 16% of all reported adverse vaccine/drug events.

(2) E-mail from the senior author to GDN: "The category 'mixed vaccines' includes vaccines containing live and inactivated strains, and vaccines containing bacteria and viruses. It is a useful classification for a broad approach such as in the Veterinary Record, but more specific categories are recorded in our database. In reply to your question about injection site sarcoma, we can find no statistically significant incidence in relation to any type of vaccine, adjuvanted or not. The numbers of reports are too small and it is often difficult to obtain treatment histories for the animals involved."

Fabia Dyer, Veterinary Medicines Directorate

References (In order of occurrence)

Are We Vaccinating Too Much? J Amer Vet Med Assoc. 1995;207(4):421-424.

Kirpensteijn J. Feline injection site-associated sarcoma: Is it a reason to critically evaluate our vaccination policies? Vet Microbio. 2006;117:59-65.

Gobar GM, Kass PH. World Wide Web-based survey of vaccination practices, postvaccinal reactions, and vaccine site-associated sarcomas in cats. J Amer Vet Med Assoc. 2002;220(10):1477-1482.

Fischer SM, Quest CM. Dubovi EJ, et. al. Response of feral cats to vaccination at the time of neutering. J Amer Vet Med Assoc. 2007;230(1):52-58.

Ford R. Recombinant Technology. Clinician's Update. N Amer Vet Assoc. 2006;3.

Richards JR, et. al. Vaccine-Associated Feline Sarcoma Task Force: Roundtable Discussion. The current understanding and management of vaccine-associated sarcomas in cats. J Amer Vet Med Assoc. 2005:226(11):1821-1842.

Banerji N, Kanjilal S. Somatic alterations of the p53 tumor suppressor gene in vaccine-associated feline sarcoma. Amer J Vet Res. 2006;67(10):1766-1772.

Kass PH, Spangler WL, Handrick MJ, et. al. Multicenter case-control study of risk factors associated with development of vaccine-associated sarcomas in cats. J Amer Vet Med Assoc. 2003;223(9):1283-1292.

Dyer F, Spagnujolo-Weaver M, Cooles S. Talt A. Suspected adverse reactions, 2006. Vet Record. 2007;160:748-750.