Canine infectious disease update (Proceedings)

1. Bordetella bronchiseptica…IN v. SQ

2. Canine Influenza Virus

3. Canine Leptospirosis

Bordetella bronchiseptica infection and prevention

New

While both parenteral and topical vaccines prevent signs of illness in exposed dogs, there are significant differences between the two products. First: in the only comparative challenge study published to date, it was shown that dogs vaccinated with a single dose of a topical (intranasal) vaccine were protected from infection and bacterial shedding. Dogs previously vaccinated with 2 doses of the parenteral (SQ) vaccine, then challenged with B. bronchiseptica, shed bacteria in the same concentration that control dogs did. These findings are particularly important among kennel-housed dogs. Parenterally vaccinated dogs still represent a risk to other, unvaccinated dogs.

New

While it was conventional knowledge that the onset immunity following topical (IN) vaccination was faster than parenteral vaccination, 2 studies have documented this fact in dogs challenged following initial vaccination. Onset of immunity following a single dose of IN vaccine is 72 hours (and…probably faster); onset of immunity to the parenteral vaccine, on initial dosing, does require 2 doses, at least 2 weeks apart then at least 7-10 days after the second dose. Onset of immunity following an annual 'booster' inoculation is not known. It is probably similar for both vaccines (within 7 days) after a single dose.

New

Conventional recommendations for B. bronchiseptica re-vaccination (booster) have been anecdotally reported as "every 6 months in dogs with sustained risk of exposure". However, until recently, there have been no studies that confirmed or refuted that information. Conventional challenge studies with the topical vaccines have shown 12 to 14 month duration of protective immunity. Based on these studied, "annual booster" seems appropriate for most dogs. It is this author's opinion that booster inoculations every 6 months for dogs facing frequent (weekly) exposure (dog day-care, frequent trips to dog parks, boarding, etc) are justified twice yearly. Dogs with minimal risk of exposure need only be vaccinated annually.

Canine Influenza Virus (CIV) infection

The clinical disease

In January 2004, an outbreak of respiratory disease occurred in 22 racing greyhounds at a Florida racetrack. Since then, dogs, mostly in shelter environments throughout the US have been confirmed with CIV infection.

Two clinical syndromes are reported:

1. a mild cough, with fever, lasting 10-14 days with subsequent recovery (14 dogs), and…

2. peracute death associated with extensive lower respiratory tract hemorrhage (8 dogs…36%) involving the lungs, mediastinum, and pleural space. Histology of the lungs revealed suppurative bronchopneumonia as well as bronchiolitis, and tracheitis.

3. about 10% or so of cases are sub-clinical…dogs are infected yet do not develop clinical signs and remain healthy. Subclinical infections appear to be common among infected dogs today.

Canine influenza is NOT a highly fatal disease; 80% of infected dogs develop nasal discharge, cough, mild fever and recover spontaneously. Several others will show NO CLINICAL SIGNS whatsoever. What makes this disease particularly problematic, clinically speaking, is the fact that it is contagious from dog-to-dog. Susceptibility rates, obviously, are very high.

Co-infection with other viruses and/or bacteria have not been studied. CIV infection in a dog with concurrent bacterial infection (B. bronchiseptica would be a likely candidate!) of the lower respiratory tract could pose a significant health threat to the affected dog(s).

Mortality in dogs is estimated to be from 6% to 8%. In clinical practice, this number may be much lower.

Occurrence of Canine Influenza in Dogs

Blood samples collected from 70 dogs with respiratory disease in shelters in Florida and a variety of veterinary practices in Florida and New York City showed 97% were positive for antibody to the influenza virus (ie, past exposure). This study demonstrated that canine influenza virus infection was not unique to the greyhound breed. Over 30 States and the District of Columbia have confirmed infections in dogs…shelter-housed dogs predominate.

Clinical Diagnosis of Canine Influenza Virus

Serology (acute and convalescent antibody titers-approx $20 per sample) is the primary tool used to establish a diagnosis in dogs. Several laboratories offer serology testing (antibody titers) as a diagnostic test. HOWEVER, it must be noted that the clinical disease is short…about 10 days to 2 weeks, and the period of virus shedding is even shorter…about 8 days. It is therefore highly unlikely that the infection can be 'diagnosed' prior to the time the disease spontaneously resolves.

Treatment

Supportive care with a broad spectrum antimicrobial is indicated to manage the risk of secondary bacterial bronchopneumonia (suggest: doxycycline, amoxicillin-clavulanic acid, azithromycin, or a fluoroquinolone). The accumulation of fluid in the pleural space, although regarded a grave prognostic sign, should be removed via thoracocentesis. Care should be taken to properly dispose of materials (endotracheal tubes, catheters, needles, syringes, oxygen tubing, etc.).

Vaccine

In July 2009, the first vaccine for CIV was released (Intervet Schering-Plough). This is a killed, adjuvanted vaccine licensed (conditional) for use in dogs only. It is important to understand that while the vaccine has been shown to mitigate the severity of clinical signs in challenged dogs and reduce the shedding of virus following exposure, the vaccine does not prevent infection, clinical signs, nor does it prevent shedding. Vaccinated dogs are expected to have a milder, short course of infection and will shed for fewer days than a dog that is immunized. The CIV vaccine, therefore, characterizes "non-sterile" immunity.

Considering infection risk (very low) among individual household pet dogs, routine vaccination of all dogs with the CIV vaccine is not recommended. NOTE: The CIV vaccine has NOT been reviewed by the AAHA Canine Vaccine Task Force. My personal opinion is that it will be categorized as NON-Core. AT ISSUE FOR SHELTERS…because 2 doses, 2 weeks apart, of this vaccine are required to induce an immune response, shelter-housed dogs do not reside in the facility long enough to derive any benefit from 2 doses of vaccine.

Other indications for the vaccine do include (my opinion) extended stay (no-kill) shelters, private research kennels that allow introduction of new dogs, and selected boarding facilities. The only issue with veterinarians recommending or mandating the CIV for clients to board dogs in the hospital is that 2-doses are required. Immunity develops by about 10 days after the second dose is given.

Duration of immunity to the CIV vaccine is not known. Annual re-vaccination (booster) is recommended by the manufacturer.

Leptospirosis

Leptospirosis is a gram negative, worldwide zoonotic infection. All mammals are susceptible. Transmission rates are very high with only 10 organisms needed to cause infection and disease. Almost all species of mammal are susceptible – there are over 250 serovars. 10 serovars are known to infect dogs and cause clinical illness. Today, vaccines are available against only 4 serovars. Vaccine cross protection is not considered significant.

On the other hand, incidental hosts, ie, humans, are epidemiologically irrelevant in outbreaks because they are usually short term hosts with acute severe disease; all ages are susceptible. The organism is cleared as the host recovers and urinary shedding is short term. Incidental hosts, following infection, produce high titers and are relatively easy to detect if illness ensues.

The route of infection of leptospirosis is either direct or indirect through contact with urine (especially through mucous membranes). The actual infectious dose is not known, although the organisms are highly infectious and can spread through tissues rapidly.

Pathogenesis

Within 15-20 minutes after being deposited in the eye – organisms can be found in blood. A low-level bacteremia develops after which it spreads to liver, kidney, spleen, etc. The antibodies that do develop are effective at clearing the organism from the tissues. In the incidental hosts the antibodies are so effective they can completely clear the organisms making diagnostic confirmation problematic. In addition, Leptospires can be transmitted across the placenta. In maintenance hosts – the antibodies clear the organisms from spleen, etc. but leave organisms in select sites like the kidney, which leads to long-term shedding.

Clinical Infections in Dogs

First described in 1899, in dogs, the serovars L. icterohemorrhagiae and L. canicola represented the predominant infecting serovars. Such infections were common in the US throughout the 70's and 80's. However, most authors agree that the frequent use of vaccines against these common serovars has effectively reduced the disease prevalence. In the mid to late 1980s, leptospirosis in dogs reemerged with the principle serovars being reported as: L. grippotyphosa, L. pomona, and L. bratislava.

Clinical presentations of infected dogs typically, although not always, involves young, large breed dogs presented for acute onset lethargy and significant fever (103° to 104° F). Muscle pain, vomiting, and dehydration are common. Acute onset icterus in a young, outdoor dog always places leptospirosis at the top of the differential diagnosis list. Other signs include bleeding diathesis, tachypenia, cardiac arrhythmia, and shock (vascular collapse). A sub-acute form of clinical leptospirosis is reported in dogs presented for renal failure, with no known predisposing cause. Affected dogs will also have high fever, myalgia and even hyperesthesia.

Hematologic findings typically include leukocytosis and thrombocytopenia. Several significant biochemical abnormalities may be detected in the same patient: azotemia (or uremia), elevated ALT and alkaline phosphatase, hyperamylasemia (with concurrent increase in lipase), and hyperbilirubinemia. Abdominal ultrasound exam may be consistent with intussusception, acute renal failure (large kidneys), and pancreatitis.

1. Microagglutination Test (MAT) – the 'gold standard' test used in the US and throughout the world, Human and Veterinary. Specific, but difficult to standardize, insensitive for some serovars, and vaccinated animals cause False + results.

2. Urine Dark Field – RARELY helpful…too many false + results ; not recommended.

3. Histolopathology – insensitive diagnostic test because biopsies are seldom representative of infected tissue.

4. Culture: difficult to perform and is not recommended.

5. PCR – is not serovar specific but is recommended by most authors today. PCR on BLOOD (early infection) and PCR on fresh urine (late); patients treated with antibiotics may have a False NEG test result. Simultaneous submission of blood and urine is recommended.

New

under development at this time is an ELISA-based rapid (Point-of-Care) assay for in-clinic use in diagnosing Leptospirosis infection in dogs. This rapid assay, when available, will offer the first opportunity for veterinarians to perform same-day testing for leptospirosis (the test will NOT verify the infecting serovar).

Treatment

"initial" treatment with amoxicillin is not required…just use doxycycline @ 5 to 10 mg/kg, PO, bid, for 2 weeks. Management of underlying kidney and/or renal disease is a must. 10-30% die. Post recovery: L. canicola – dogs shed from months to years. L. icterohemorrhagiae – dogs shed several months, other serovars – dogs shed 3 weeks to a month.

Vaccination

recommendations outlined in the 2011 ACVIM consensus statement indicate use of the 4-way vaccines only when protection is indicated. Leptospirosis is categorized as a NON-CORE (or "optional") vaccine. The vaccine is effective in reducing clinical signs caused by the infecting serovars provided in the vaccine. There is no cross-protection among the various serovars in the vaccine.

2 initial doses are required; annual boosters are recommended for dogs deemed to be at risk

New

the duration of immunity to the Recombitek (Merial) leptospirosis vaccine is 15.5 months for L. gripposyphosa. 12 month DOI data is available for L. canicola and L. icterohaemorrhagiae. This is the only Leptospirosis vaccine with a label claim for DOI.

New

Although Leptospirosis vaccine do mitigate clinical signs following infection, vaccines have not consistently been shown to prevent infection and shedding in vaccinates that were subsequently exposed. The Recombitek (MERIAL) is the only leptospirosis vaccine with a label claim for prevention of infection and shedding for the serovars: L. canicola; L. icterohaemorrhagiae; L. grippotyphosa.

References

Ford RB: Bordetella bronchiseptica: Beyond Kennel Cough. Chpt 147 in Bonagura JD and Twedt DC (eds): Current Veterinary Therapy XIV. Saunders-Elsevier. 2009. pp.646-649.

Ford RB: Bordetella bronchiseptica has zoonotic potential. Topics in Vet Med 1995; 6:18-22.

Davis R et al. Comparison of the mucosal immune response in dogs vaccinated with an intranasal avirulent live culture or a subcutaneous antigen extract vaccine of Bordetella bronchiseptica. Vet Therap. 8:32, 2007.