Infectious disease update (Proceedings)

     • Bordetella bronchiseptica...IN v. SQ

     • Canine Leptospirosis

     • Canine Influenza Virus

1. Bordetella bronchiseptica vaccination: IN or SQ?

Closely related to Bordetella pertussis, the cause of "whooping cough" in humans, Bordetella bronchiseptica is a gram negative, aerobic coccobacillus particularly well adapted to colonize the ciliated respiratory epithelium of dogs and cats. (NOTE: it's known today that B. bronchiseptica is the progenitor of all 9 recognized Bordetellae). Today, this organism is regarded as a principle etiologic agent in what is now being termed "canine infectious respiratory disease" or CIRD (the term canine infectious tracheobronchitis (ITB) is 'out'). In the clinical setting, however, B. bronchiseptica infection should not be regarded as synonymous with CIRD. Dogs infected with canine parainfluenza virus (CPiV), canine influenza virus (CIV), or canine adenovirus-2 (CAV-2) are expected to experience more severe respiratory disease when co-infected with B. bronchiseptica than with any these agents alone. Canine bordetellosis, i.e. B. bronchiseptica infection in the absence of either CPiV, CIV, or CAV-2, is known to occur and can be associated with acute, fatal pneumonia in young dogs. B. bronchiseptica is transmitted through aerosolization of respiratory secretions. Bacteria can also be transmitted directly by contaminated dishware, human hands, and other fomites. Because B. bronchiseptica possesses several intrinsic mechanisms for evading host defenses, it is recognized for its role as a significant complicating factor in dogs with multiple-agent respiratory infections.

      Vaccination

Several commercially licensed canine vaccines for protection against B. bronchiseptica, CAV-2, and CPiV are available. At this time, there is only one vaccine licensed for protection against feline B. bronchiseptica infection. Canine vaccines are available for topical (intranasal); currently there is only one parenterally administered vaccine for protection of dogs against B. bronchiseptica. Regardless of the route of administration, vaccinated dogs experience substantially less coughing when compared to control dogs following bacterial challenge. Beyond that, however, recent studies conducted on B. bronchiseptica vaccine since 2005 have shed new light on existing products and (fortunately) provided good clinical evidence to refute old paradigms.

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.

Another fact that generally favors topical vaccine over parenteral vaccine is the fact that parainfluenza virus (CPiV) is combined with virtually ALL topical vaccines currently on the market today. In fact, most authors agree that the best way to protect against parainfluenza virus infection (the infection that best characterizes the disease called "Kennel Cough") is via topical (also called, IN or intranasal) vaccination. Parenteral (SQ) vaccination against CPiV induces no mucosal (or local) immunity.

2. Leptospirosis: The 2-Way? The 4-Way? ...Or The "No Way"?

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. All pathogens belong to the genus Leptospira. There is tremendous geographic variation in prevalence of serovars: The United States has 6-7, Latin America has 15-20, while Scandinavia has a number of unique serovars not typically seen in the US. The maintenance host (typically wildlife) does not become clinically ill despite the fact that organisms are sustained in the kidneys and shed months to years or for the life of the animal. Natural hosts do not make significant antibody titers when infected. Immediately following infection, there is a significant rise in Antibody followed by a rapid decline. In addition, leptospires can be maintained in the liver of wildlife hosts. Different species show differences in pathogenesis (raccoons are more susceptible than dogs).

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. They can cross the placenta and infect fetuses. Any damaged skin allows entry.

Vaccination: Recommendations of the AAHA Canine Vaccine Task Force, to be published in Sept 2010, categorize leptospirosis as a NON-CORE (or "optional") vaccine. It is regarded by many as the most reactive vaccine used in dogs and, as such, should only be administered to dogs with a reasonable risk of exposure or dogs that reside in geographic locations where confirmed cases of leptospirosis have been recognized. Immunity is serovar specific (there's NO cross protection); need at least 2 initial doses and boost once per year. Duration of immunity to all leptospirosis vaccines is (in fact) approx. 12-14 months following the initial 2-dose series. NOTE: the Microscopic Agglutination Titer (MAT) conventionally used to establish a diagnosis is NOT reflective of immunity...MAT titers do rise following vaccination but tend to fall quickly.

There is a need for less reactive vaccines. Do we need to vaccinate? Yes...when and where the risk is established. Some have stipulated that there is a re-emergence of leptospirosis...still, cases are uncommon. There is no evidence that the 4-way vaccines are less reactive than the 2-way vaccines.

Does zoonotic potential of Leptospirosis justify vaccination? All of the leptospirosis vaccines currently available today mitigate clinical illness the dog following exposure...vaccination does NOT consistently prevent infection nor shedding! NEW: a recently licensed (4-servar) Leptospirosis vaccine (Merial) is expected to be available Fall 2010 (release date is predicated on developing sufficient inventory). Uniquely, the product label indicates 100% of dogs, following administration of 2-doses, were protected following challenge. Spirochetes were not found in the kidneys of vaccinated dogs following challenge..suggesting this vaccine induces a 'sterile' immunity to leptospirosis.

New: at least it's in the works...currently under development is an ELISA-based rapid assay ('SNAP' test, IDEXX Laboratories) for in-clinic use in diagnosing Leptospirosis infection in dogs. This rapid assay, when available, offers the first opportunity for veterinarians to perform same-day testing for leptospirosis (the test will NOT verify the infecting serovar).

3. Canine Influenza Virus (Civ) Infection

In 2009, several television and newspapers reports addressed, in only ways that the media can, recent research findings that confirmed the fact the equine influenza virus 'jumped' species and had infected dogs. Subsequent studies confirmed the ability of this virus to be transmissible among dogs.

[Primary Investigators: Dr. P. Cynda Crawford, University of Florida, College of Veterinary Medicine, Gainesville, FL; Dr. Ed Dubovi, Cornell University, College of Veterinary Medicine, Ithaca, NY.]

The Facts:

The Clinical Disease: In January 2004, an outbreak of respiratory disease occurred in 22 racing greyhounds at a Florida racetrack. Two clinical syndromes were 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 broncho-pneumonia 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.

In a summary statement to the CDC, Dr. Crawford points out that canine influenza is NOT a highly fatal disease, indicating that 80% of infected dogs develop nasal discharge, cough, mild (to no) fever and recover spontaneously. Several others will manifest 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.

Virus Identification: After considerable research, it was (recently) confirmed that interspecies transmission of an entire equine influenza A (H3N8) virus (documented as a cause of equine respiratory disease for over 40 years) to the dog [ie, the virus sequence corresponds with the H3 hemagglutinin and the N8 neuraminidase subtype]. What's more, investigators at U of FL examined archival lung tissue from greyhounds that died from hemorrhagic bronchopneumonia in March 2003. Sequence analyses of virus isolated from lungs indicated that viruses had infected greyhounds prior to 2004. Further studies comparing the equine and canine influenza viruses have shown that only 4 amino acid changes differentiate the two viruses.

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). Today, over 30 States and the District of Columbia have confirmed infections in dogs...shelter-housed dogs predominate. In fact, infection is likely to have occurred in even more States than recently reported.

Transmission: Experimental studies in dogs suggest that virus will persist in the nasal cavity and oropharynx of challenged dogs and suggests that shedding is possible. Dog-to dog transmission could occur via large aerosolized droplets from the upper respiratory tract, fomites, or direct mucosal contact.

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. Antibody titers obtained during the course of clinical disease are likely to be NEGATIVE; expect titers to rise 3-4 weeks following the initial onset of signs (hence the need for acute and convalescent titers.)

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 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. My discussions with the researchers at Intervet/Schering Plough would agree. Indications for vaccination are perhaps best left to shelter-housed dogs where the threat of infection is clearly higher. HOWEVER, AT ISSUE FOR SHELTERS...at least 2 doses of this killed vaccine are required to induce an immune response. One dose will not induce protective immunity. In the typical shelter setting, most dogs do not even reside in the facility long enough to derive any benefit from vaccination.

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 2-3 weeks after the second dose is given.

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

Zoonotic potential: There is NONE.