Infectious Disease UPDATE

Infectious Disease UPDATE

Richard B. Ford, DVM, MS

Emeritus Professor of Medicine

North Carolina State University

Bordetella bronchiseptica vs. CIRD

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. Today, this organism is regarded as a principle etiologic agent in what is now being termed “canine infectious respiratory disease” or CIRD (the term “Kennel Cough” 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

Commercially licensed canine vaccines for protection against B. bronchiseptica are available for 1) parenteral administration, 2) intranasal administration (usually in combination with parainfluenza virus and/or adenovirus-2). At this time, there is only one vaccine licensed for protection against felineB. bronchiseptica infection.

Regardless of the route of administration, vaccinated dogs experience substantially less coughing when compared to unvaccinated (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: In the only comparative challenge study published to date, it has been shown that dogs vaccinated with a single dose of a topical (intranasal) vaccine ora single dose ofthe oral Bordetella vaccine were protected from clinical infection and bacterial shedding following challenge. Dogs previously vaccinated with 2 doses of the parenteral (SQ) vaccine, then challenged with B. bronchiseptica, experience a reduction in clinical signs: cough and nasal discharge. The reduction in clinical signs was judged to be less than that experienced by dogs vaccinated by either the intranasal or the oral route. Dogs vaccinated by injection continued to shed bacteria from the respiratory tract in the same concentration that control dogs did. These findings are particularly important among kennel-housed 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 within 72 hours (and…possibly by 48 hours); onset of immunity to the parenteral vaccine, on initial dosing, does require 2 doses, 2 to 6 weeks apart then around 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. The duration of immunity subsequent to vaccination by the parenteral, and the oral, routes is not known.

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.

NEW

The oral Bordetella bronchiseptica vaccine (BronchiShield ORAL, Boehringer Ingleheim), introduced in 2012, has only recently been subjected to independent comparative studies against IN and parenteral products. Initial reports from veterinarians indicate that the vaccine is easy to administer and is well tolerated by dogs during administration. The vaccine appears to induce a protective mucosal immune response (likely due to secretory IgA) that is comparable to that induced by a single dose of intranasal vaccine.

As is the case with most IN vaccines, the oral vaccine is sold in a vial that is similar to those intended for parenteral administration. Veterinarians are encouraged to label (in the refrigerator) this product in a way that will prevent the risk of inadvertent administration by the parenteral or intranasal routes.

CANINE LYME DISEASE…How Real the Threat?

Prevalence & Distribution

Canine Lyme borreliosis is not a reportable disease; therefore, precise estimates of disease prevalence in the US & Canada are unavailable. However, compared with humans, dogs in endemic regions are at substantially greater risk for exposure to infected ticks. Surveillance reports of dogs with positive antibody test results suggest that up to 85% of dogs living in endemic areas are at risk for B burgdorferi infection.

Endemic Regions in Canada

Results of surveillance studies in the U.S., Canada, and Europe designed to monitor the spread of infected ticks indicate that both climate change and migratory ground-feeding birds contribute to movement of infected ticks and increased risk for human and animal exposure.4-6 These studies highlight the importance of continued surveillance—through routine testing of dogs living in regions where the risk for exposure to Ixodes species ticks is high.

In Canada….

The Diagnostic Dilemma

Results of surveillance studies in the U.S., Canada, and Europe designed to monitor the spread of infected ticks indicate that both climate change and migratory ground-feeding birds contribute to movement of infected ticks and increased risk for human and animal exposure. These studies highlight the importance of continued surveillance—through routine testing of dogs living in regions where the risk for exposure to Ixodesspecies ticks is high.

In human medicine, diagnosis of Lyme disease centers on:

1.Manifestation of signs and symptoms consistent with Lyme disease

2.History of possible exposure to Ixodes ticks

3.Positive test result on both an enzyme immunoassay (or immunofluorescence assay [IFA]) and an immunoblot test (Western blot). Although , the C6 antibody test (same technology used in the IDEXX Snap test and Quant C6), has been licensed for use in humans (United States) and, ALONE, is the preferred diagnostic test for humans in some States.

Treatment is indicated only when all 3 criteria have been documented.

In veterinary medicine, it must be emphasized that there is no single pathognomonic diagnostic test for canine Lyme borreliosis.

For over 10 years, point-of-care testing (SNAP 4× and SNAP 4D× Plus, idexx.com) have been available to detect antibodies to the highly conserved C6 peptide of B. burgdorferi. With high sensitivity and specificity, this rapid assay is an excellent surveillance tool for identifying dogs that are infected, not simply “exposed”, with B. burgdorferi, and is particularly valuable to screen dogs within areas where Lyme disease is emerging. None of the commercial Lyme disease vaccines cause false positive C6 test results. A positive test, however, cannot be used to predict the clinical outcome of an infected dog.

Clinical & Laboratory Assessment

Simply identifying antibodies to B burgdorferi in a dog does not constitute a clinical diagnosis of Lyme borreliosis. Before establishing a diagnosis of Lyme borreliosis, the clinician must:

• Consider physical and laboratory findings (Table 1)
• Determine whether or not the dog resides in, or has traveled to, a region inhabited by the Ixodes tick.

Laboratory Assessment. The laboratory assessment of any patient found to have serum antibodies against B.burgdorferi should include:

• Hematology
• Serum biochemistry profile
• Urinalysis
• Urine protein:creatinine ratio (UP:UC), to assess proteinuria.

Vaccination of Seropositive Dogs

Because natural infection does not induce protective immunity, it is reasonable to recommend vaccination of seropositive dogs, particularly those living in endemic regions, to prevent re-infection. If a seropositive dog manifests clinical signs, vaccination may be given following completion of the recommended treatment period. If clinical signs are not present, vaccination may be administered at the time of testing. There is no known therapeutic value associated with vaccinating a seropositive dog.

Lyme Borreliosis is a Disease to Prevent—Not to Treat

The reasons are clear:

• Cost of treatment and post treatment monitoring can be significant for the pet owner.
• Antimicrobial treatment, regardless of the drug used, is not expected to clear bacteria from tissue, and therapy is not entirely free of adverse consequences.
• Health consequences of long-term infection, particularly dogs subject to re-infection, are unknown.
• Natural immunity to B burgdorferiis short-lived and does not provide significant or sustained protection for pets re-exposed to infected ticks.

LEPTOSPIROSIS

Leptospirosis is a worldwide zoonotic infection caused by a gram-negative bacterium (spirochete). Virtually all mammals are susceptible. Transmission rates are very high with only 10 organisms needed to cause infection and disease. Of the 250+ serovars recognized, North America has 9 or 10, Latin America has 15-20, while Scandinavia has a number of unique serovars not typically seen in the US or Canada.

In order to persist in nature, leptospires need a maintenance host, a role that humans do not serve. Leptospirosis has actuallybeen regarded as a relatively minor infection in humans and, for the past 20 years, has not been regarded as a “reportable infection”. Today, however, the increasing numbers of cases of human leptospirosis (US) have prompted the Centers for Disease Control (CDC) to reconsider that position and may re-instate leptospirosis as a reportable disease. Leptospirosis appears to be on the rise in both humans and animals.

POINT: among practicing veterinarians in North America, the risk for exposure is greater among Small Animal practitioners than Large Animal practitioners.

PATHOGENESIS:

The actual infectious dose is not known, although the organisms are highly infectious and can spread through tissues rapidly. Within 15-20 minutes after being deposited in the eye – organisms can be found in blood. A low-level bacteremia develops and quickly spreads to liver, kidney, spleen, etc. In maintenance hosts (eg, L. canicolain dogs) – the antibodies clear the organisms from spleen, etc. but leave organisms in select sites like the kidney, which can lead to long-term shedding.

RISK for INFECTION-what it used to be:

For years, it has been published and taught that the risk for leptospirosis infections was greatest among young, large breed dogs that live on farms or in rural setting where access to free-standing water is prevalent.

RISK for INFECTION-what it is today:

For the last 20 years, studies have consistently shown an increase in clinical leptospirosis among small breed, backyard dogs, especially among the terrier breed. WHY the shift? Probably because veterinarians, concerned about vaccination reactions with the leptospirosis vaccine, didn’t vaccinate small breed dogs.

Important for veterinarians practicing in the Northeastern US and Eastern Canada, there is a seasonal peak of canine leptospirosis that occurs in these regions in the Fall (especially October and November). Although infections can occur at any time of year…practices that do recommend vaccination may want to emphasize administration of booster doses in the later summer…immune “memory” is not well sustained against bacterial infections.

Other risk factors to consider include dogs that spend a significant amount of time outdoors (even if in their own yard), young dogs are at greater risk than older dogs, and (although not exclusively) access to free-standing water.

DIAGNOSTICS:

Leptospires target endothelial cells…liver and kidney especially, but also vascular endothelium (think lung and eye as well).

Acute onset lethargy and significant fever (103° to 104° F) are common. Muscle pain, vomiting, and dehydration are often seen on physical examination.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 andespeciallyalkaline phosphatase, hyperamylasemia (with concurrent increase in lipase), and hyperbilirubinemia. Abdominal ultrasound exam may be consistent with intussusception, acute renal failure (large kidneys), and pancreatitis. Lots of laboratory tests are available but, still, offer limited information:

1. Microagglutination Test (MAT) – the “gold standard‟ diagnostic test used in humans and animals throughout the world. Is difficult to run and subjective to interpret. And although touted as the test used to determine the infecting serovar…it is actually quite inaccurate at doing so (significant cross-reactivity due to molecular mimicry).

2. Urine Dark Field – RARELY helpful; not sensitive as a clinical test.

3. Histopathology – although used in the post-mortem diagnosis, is an insensitive diagnostic test.

4. Culture is difficult, expensive, can take months to complete.Is not practical in the clinical setting.

5. PCR (preferred) – sensitive (can detect withfewer than 100 organisms) – But, is not serovar specific (not that it really matters to the clinician). This is offered by more commercial and university laboratories today. Is usually performed on fresh urine (acute stages)and serum (later stages), simultaneously. Results seem to do well in defining LEPTO vs. Not-LEPTO. Downside…samples must be sent out and results may require a few days.

Point of Care Testing:

IDEXX Laboratories (in 2015) licensed a Rapid-Assay (SNAP Test) for the detection of Leptospirosis antibody (IgG) in dogs.

Last year, Zoetis licensed another point-of-care test for leptospirosis antibody (IgM).

There are drawbacks to both tests: namely FALSE-Negative tests…ie, the dog is acutely ill and presented for examination, but detectable levels of antibody have not yet been produced. And, FALSE-Positive test results…prior vaccination can and does interfere, especially with the IgG test for longer than was initially anticipated.

The value of Point-of-Care testing is in the patient with a clinical history and physical findings consistent with leptospirosis, but has never been vaccinated. If the test is POSITIVE, the dog is likely infected. (Remember: leptospira antibody is an indication of INFECTION…not PROTECTION.

Updated: March 2018