Vaccinations in Atypical Veterinary Patients

Vaccines are labeled for use in healthy patients only, but dogs and cats with chronic or acute health concerns are commonly presented for vaccination.

Ask the Expert: When should vaccines be administered in dogs and cats with health concerns?

The decision to vaccinate unhealthy or atypical patients should be based on whether an appropriate immune response is possible and whether risk for adverse effects is increased. Because vaccine trials typically include only healthy animals, administering vaccines to patients with health concerns is extra-label use and based on clinical discretion. Vaccine safety concerns should be balanced with risk for individual exposure and extent of previous vaccinations.

Causes of immunocompromise include infectious disease, congenital disease, autoimmune disease, neoplasia, medication, and malnutrition. The importance of vaccinations is increased in immunocompromised patients, as they are at risk for severe sequelae from infection; however, the ability to mount an effective immune response to vaccines may be decreased. A patient’s individual immune response should be assessed before recommendations are made, and pet owners should be informed that response to immunization is not guaranteed.

Commercially available small animal vaccines are generally safe and have low rates of adverse effects,¹ but protocols for limited vaccination or no vaccination should be considered in patients with a history of significant adverse vaccine reactions or autoimmune disease.

Pathogenicity can also be a concern when modified live virus (MLV) vaccines are used extra-label or in immunocompromised patients, as attenuated pathogens in these vaccines may induce illness (rare) in patients with abnormal immune function or other risk factors. For vaccines like feline herpesvirus/calicivirus/panleukopenia that are commercially available in both modified live and killed forms, the killed vaccine may be safer for immunocompromised patients.²

Identification of Patients With Health Concerns

Patient health should always be evaluated prior to vaccination, including review of current medications, medical conditions, previous adverse vaccine reactions, and pregnancy status. Minimum assessment should ideally include energy level, mucous membranes (hydration, color, and capillary refill time), readily accessible lymph nodes, and presence of oculonasal discharge.

Infectious Disease

Poor response to vaccination and worsened illness due to stress of vaccination are concerns in patients with infectious disease; however, the CDC Advisory Committee on Immunization Practices does not consider mild acute illness with or without fever a contraindication for vaccination in humans, and the 2022 AAHA canine vaccination guidelines state shelter dogs with mild illness may be vaccinated.^3,4 Vaccines can be readministered after several weeks when the patient is healthy if there is concern illness prevented an appropriate immune response. Vaccination should be deferred until illness is resolved if a patient has moderate to severe illness or the owner prefers a conservative approach.

Autoimmune Disease

Patients with active autoimmune disease should not be vaccinated until clinical signs are controlled. The decision to vaccinate once a patient is in remission should be based on likelihood of relapse triggered by vaccination, potential severity of autoimmune disease should it recur, and risk for exposure to the disease being vaccinated against. For example, vaccination should be minimized in patients with a history of immune-mediated polyradiculoneuritis because this disease is life-threatening and can occur following vaccine administration, but routine vaccination of dogs with autoimmune thyroiditis is reasonable because most cases are not life-threatening and a relationship with vaccines has not been shown (Table).^5-7 Because veterinary research sample sizes are often small, a lack of proven connection between vaccination and a given disease does not prove vaccines are safe for a specific patient. Minimizing vaccines in patients with a history of life-threatening immune-mediated disease is therefore reasonable, even if concern for that disease is anecdotal, speculative, or only demonstrated in other species.

Table: Relationships Between Autoimmune Diseases & Vaccination

FeLV & FIV

Immune system support from vaccination is important in cats infected with FeLV or FIV, as these patients may be immunocompromised. Although a few studies found evidence of appropriate seroconversion in FIV-positive cats following vaccination, others demonstrated diminished response to virus challenge following immunization.^8-11 There is speculation that vaccine-induced immunostimulation could worsen disease in FIV-infected cats, although clinical significance is unclear.² Potential for poor immune response is greater in cats with progressive FeLV infection, as these cats may be significantly immunocompromised. The AAFP recommends vaccinating otherwise healthy FeLV- or FIV-infected cats based on individual risk assessment and according to standard vaccine protocols.¹²

FIP

Cats infected with FIP that are actively ill should not be vaccinated. Evidence-based consensus on the best approach for vaccination of cats that survive FIP is lacking. Until better evidence becomes available, vaccine decisions for these cats should be based on risk/benefit analysis and discussion with the owner. Many clinicians opt for delayed and/or minimal vaccine protocols following resolution of FIP. The author discourages complete vaccine avoidance, as there is at least one anecdotal report of an unvaccinated cat dying of panleukopenia following successful treatment of FIP. 

Medications

Glucocorticoids

Glucocorticoids administered short term, long term at physiologic doses, or via inhaled or topical routes are not expected to interfere with vaccinations. Patients receiving long-term immunosuppressive doses of corticosteroids should be treated as immunocompromised. The CDC recommends humans receiving high-dose systemic corticosteroid therapy for >2 weeks discontinue the medication for ≥1 month before receiving MLV vaccines.¹³ The impact of glucocorticoids administered long term at anti-inflammatory doses on response to vaccines is unclear, but concerns are unlikely with low anti-inflammatory doses.²

Oclacitinib

Manufacturer data indicate puppies administered 3 times the label dose of oclacitinib and vaccinated with killed rabies virus, modified live distemper virus, and modified live parvovirus adequately seroconverted to all 3 viruses; however, 2 out of 8 puppies failed to seroconvert to vaccination with modified live canine parainfluenza virus.¹⁴ At label doses, oclacitinib has been widely used in dogs without apparent interference with vaccination, but care should be taken in patients with other risk factors for immunocompromise. Safety and efficacy of vaccines in cats receiving oclacitinib have not been evaluated.

Ilunocitinib

The manufacturer of ilunocitnib advises against administering vaccines during or within 28 days of treatment due to risk for fatal vaccine-induced disease from MLV vaccines and inadequate immune response to any vaccine.¹⁵

Chemotherapy

Safety and efficacy of vaccines in small animals receiving chemotherapy have not been evaluated. In humans, only specific inactivated vaccines are recommended during chemotherapy. Administering vaccines ≥14 days prior to chemotherapy or 3 to 6 months after completion of treatment is preferred, but a patient’s degree of immunosuppression and risk should guide decision-making.¹³ If vaccinations are necessary during treatment, killed vaccines should be selected over MLV.

Antibiotics

Antibiotics do not interfere with efficacy of most vaccines but may kill vaccinal bacteria in mucosal attenuated live Bordetella bronchiseptica vaccines for dogs or cats, interfering with vaccine effect.

Cyclosporine

Cyclosporine is commonly used in dogs and cats for treatment of a wide array of conditions, many of which (eg, perianal fistulas, atopic dermatitis) require long durations of treatment. Although these diseases may not be severe enough to contraindicate vaccination, cyclosporine has immunosuppressive properties that may diminish immune response to vaccines. Cyclosporine use is not a contraindication for administration of killed vaccines (eg, rabies), but the manufacturer recommends avoidance of MLV vaccines during therapy.^16,17

Anesthesia

Studies have demonstrated that vaccination at the time of spay or neuter surgery results in an excellent immune response, despite concern that concomitant administration of vaccines and anesthesia may interfere with development of an appropriate immune response.^18-20 In order of preference, vaccines should be administered prior to hospital intake to protect against hospital-acquired infection, following anesthetic recovery to allow differentiation of rare anaphylactic vaccine reactions from anesthetic-associated complications, or at the time of surgical recovery or induction.

Patients With a History of Vaccine Reaction

Patients with a history of adverse vaccine reaction may warrant additional caution regarding future vaccinations; however, many adverse effects will not recur, even if an identical protocol is repeated. Certain perceived adverse vaccine reactions (eg, lethargy, fever, mild injection site soreness) occur as a result of unwanted but physiologically appropriate immune system responses to vaccines. In these cases, administering a different brand of vaccine, separating administration of multiple vaccines, or administering premedication (eg, single dose of an NSAID, anti-inflammatory dose of a corticosteroid) may prevent further concerns. In contrast, patients with a history of true, nonphysiologic adverse vaccine reactions (eg, hypersensitivity reaction) warrant careful attention. The decision to vaccinate should be based on the type of reaction, importance of the vaccine (eg, risk for exposure, severity of disease), and severity of the previous reaction.

Histamine-Mediated (Type I Hypersensitivity) Reactions

Patients that experience vaccine-associated anaphylaxis involving cardiac arrest should no longer receive vaccines. Patients that experience uncomplicated facial edema, urticaria, or mild vomiting following vaccination may not experience recurrence; administration of a different brand of vaccine, administration of no more than one vaccine per day, premedication with diphenhydramine (2-4 mg/kg PO or 0.5-2 mg/kg IM), and/or premedication with dexamethasone (0.1 mg/kg IM or IV; the value of corticosteroids in preventing histamine-mediated reactions is controversial) should be considered as precautions. If a patient with a history of life-threatening anaphylaxis must be vaccinated, the patient should have an IV catheter placed in advance and be hospitalized under direct supervision for ≥8 hours following vaccination with emergency (eg, crash cart) supplies readily available.

Antibody titers against canine distemper virus, adenovirus, parvovirus, and feline panleukopenia virus may be considered to minimize frequency of core vaccine administration in at-risk patients.^a Single-virus vaccines (eg, canine distemper, parvovirus) are not necessarily safer than combination products, as type I hypersensitivity reactions are often triggered by exogenous proteins in vaccines rather than the viral component(s) of the vaccine.^21,22

Reproductively Active Patients

When possible, patients intended for breeding should receive appropriate immunizations prior to becoming pregnant. Vaccination of pregnant and lactating patients is generally extra-label use and should only be performed in situations where the benefits outweigh the risks. Modified live canine distemper virus/adenovirus type 2/parvovirus (DAP) and feline herpesvirus/calicivirus/panleukopenia virus vaccines can induce adverse effects in neonates, including encephalitis, myocarditis, and cerebellar hypoplasia.²³ Administration of MLV vaccines should be delayed in puppies and kittens until at least 4 to 6 weeks of age. In high-risk situations, however, pregnant patients may be vaccinated; for example, the 2022 AAHA canine vaccination guidelines indicate modified live canine DAP vaccines are appropriate for pregnant dogs housed in shelters.³ If vaccination of a pregnant cat is necessary, a killed feline herpesvirus/calicivirus/panleukopenia virus vaccine is preferred over MLV.²⁴

Breed Concerns

Many breed-related vaccination concerns are scientifically unfounded, but a few warrant specific attention.

Wild Species Hybrids

Wild species hybrids, including wolfdogs, Bengal cats, and Savannah cats, present several vaccination concerns. Certain jurisdictions may not recognize rabies vaccines administered to hybrid animals because the vaccines are not labeled for use in exotic canine and feline species. Similarly, vaccine efficacy may not be guaranteed by manufacturers because vaccines are not tested for efficacy in species not listed on the label. Familiarity with regional laws and recommendations of specific vaccine manufacturers is important when treating hybrid patients (see Suggested Reading).  

Rarely, MLV reversion to virulence has been reported following vaccination of certain wild species not listed on the label, including distemper and adenovirus in foxes and wolves and herpesvirus and calicivirus in cats living in zoos.^25-28 Use of commercially available recombinant canine DAP or killed feline herpesvirus/calicivirus/panleukopenia virus vaccines for wild species hybrids may therefore be preferred, although many zoo and wildlife clinicians, as well as the Savannah Cat Association, find MLV vaccines acceptable in these populations.²⁹

Weimaraners

Hypertrophic osteodystrophy (HOD) is a developmental disease of the long bone metaphyses that primarily affects puppies 8 to 16 weeks of age, with most cases occurring within 3 weeks of vaccination.³⁰ HOD occurs in many breeds but has a heritable component in Weimaraners and a possible association with Weimaraner immunodeficiency syndrome.^31-33 The etiology of HOD is unknown, but association with MLV distemper vaccination has led to a theory that recombinant canine distemper vaccines are safer for Weimaraner puppies; however, one report found only 32 of 53 puppies diagnosed with HOD previously received modified live distemper vaccines and the remaining 21 received recombinant vaccines.³¹ The Weimaraner Club of America health committee advocates a limited vaccination schedule, with recombinant DAP vaccines administered at 8 and 12 weeks of age, followed by an antibody titer at 15 to 16 weeks of age to verify seroconversion.³⁴ Whether this protocol is superior and whether vaccines are related to HOD pathogenesis is unclear; owners should be reassured that most puppies will not experience adverse events regardless of vaccine choice. For immunocompromised or clinically ill puppies, vaccines should be delayed or skipped as appropriate. Puppies with Weimaraner immunodeficiency syndrome exhibit decreased immunoglobulin production and thus may not respond appropriately to vaccines, even if they are otherwise healthy enough to be vaccinated.³²

^a In most states, antibody titers cannot be used for legal proof of rabies immunity. Antibody titers are also less useful in assessing immunity against diseases for which immune response depends largely on cellular rather than humoral defenses (eg, feline herpesvirus, feline calicivirus).^24,43