Predominant risk factors for tick-borne co-infections in hunting dogs from the USA.

BACKGROUND: Both incidence and geographical range of tick-borne disease has increased across the USA. Similar to people, dogs are hosts for Anaplasma spp., Babesia spp., Ehrlichia spp. and Borrelia burgdorferi. Dogs also share our homes and beds, making them both a sentinel for the ticks in our backyards but also increasing our exposure to ticks. Measures to better track, prevent, and/or treat tick-borne diseases in companion animals can lead to better control and prevention of human tick-borne disease. This study identifies demographic and co-infection risk factors for canine seropositivity to tick-borne infections in a cohort of hunting dogs across the USA. RESULTS: Human patterns of tick-borne disease co-infection in the USA have been predominantly driven by the geographical distribution of the tick vector. Dogs who tested seropositive for Anaplasma spp. were 1.40 times more likely (P = 0.0242) to also test seropositive for Babesia spp. and vice versa (1.60 times more likely, P = 0.0014). Dogs living in the West had 5% lower risk (P = 0.0001) for Ehrlichia spp. seropositivity compared to other regions. Controlling for age and Anaplasma spp. seroprevalence, dogs in all three other regions were 2.30 times more likely (P = 0.0216) to test seropositive for B. burgdorferi than dogs in the West. Dogs seropositive for B. burgdorferi were 1.60 times more likely (P = 0.0473) to be seropositive for Anaplasma spp. CONCLUSIONS: Tick geographical distributions have a prominent impact on the regional distribution of hunting dog exposure to tick-borne diseases. Education concerning regional tick prevalence and disease risk is important for everyone, but particularly dog owners, regarding ticks in their region and protection from infection and co-infection of tick-borne pathogens as they travel or move with their dogs. Dogs are sentinel species for human exposure to ticks, and as such surveillance of canine tick-borne infections and understanding the probability that these infections might be seen together as co-infections helps predict emerging areas where people are more likely to be exposed as well.

Comorbid infections induce progression of visceral leishmaniasis.

BACKGROUND: Visceral leishmaniasis (VL) is a vector borne zoonotic disease endemic in humans and dogs in Brazil. Due to the increased risk of human infection secondary to the presence of infected dogs, public health measures in Brazil mandate testing and culling of infected dogs. Despite this important relationship between human and canine infection, little is known about what makes the dog reservoir progress to clinical illness, significantly tied to infectiousness to sand flies. Dogs in endemic areas of Brazil are exposed to many tick-borne pathogens, which are likely to alter the immune environment and thus control of L. infantum. RESULTS: A cross-sectional study of 223 dogs from an area of Natal, in the Rio Grande do Norte, Brazil, were studied to determine the association between comorbid tick-borne disease and Leishmania infection in this endemic area. The risk of Leishmania seropositivity was 1.68× greater in dogs with tick-borne disease seropositivity compared to those without (Adjusted RR: 1.68, 95% CI: 1.09-2.61, P = 0.019). A longitudinal study of 214 hunting dogs in the USA was conducted to determine the causal relationship between infection with tick-borne diseases and progression of VL. Hunting dogs were evaluated three times across a full tick season to detect incident infection with tick-borne diseases. A logistic regression model with generalized estimating equations to estimate the parameters was used to determine how exposure to tick-borne disease altered VL progression over these three time points when controlling for other variables. Dogs infected with three or more tick-borne diseases were 11× more likely to be associated with progression to clinical VL than dogs with no tick-borne disease (Adjusted RR: 11.64, 95% CI: 1.22-110.99, P = 0.03). Dogs with exposure to both Leishmania spp. and tick-borne diseases were five times more likely to die during the study period (RR: 4.85, 95% CI: 1.65-14.24, P = 0.0051). CONCLUSIONS: Comorbid tick-borne diseases dramatically increased the likelihood that a dog had clinical L. infantum infection, making them more likely to transmit infection to sand flies and people. As an important consequence, reduction of tick-borne disease exposure through topical or oral insecticides may be an important way to reduce progression and transmissibility of Leishmania infection from the canine reservoir to people.

Randomized, controlled, double-blinded field trial to assess Leishmania vaccine effectiveness as immunotherapy for canine leishmaniosis.

Better tools are necessary to eliminate visceral leishmaniasis (VL). Modeling studies for regional Leishmania elimination indicate that an effective vaccine is a critical tool. Dogs are the reservoir host of L. infantum in Brazil and the Mediterranean basin, and therefore are an important target for public health interventions as well as a relevant disease model for human VL. No vaccine has been efficacious as an immunotherapy to prevent progression of already diagnostically positive individuals to symptomatic leishmaniasis. We performed a double-blinded, block-randomized, placebo-controlled, vaccine immunotherapy trial testing the efficacy of a recombinant Leishmania A2 protein, saponin-adjuvanted, vaccine, LeishTec®, in owned hunting dogs infected with L. infantum. The primary outcome was reduction of clinical progression, with reduction of mortality as a secondary outcome. Vaccination as an immunotherapy reduced the risk of progression to clinically overt leishmaniasis by 25% in asymptomatic dogs (RR: 1.33 95% C.I. 1.009-1.786 p-value: 0.0450). Receiving vaccine vs. placebo reduced all-cause mortality in younger asymptomatic dogs by 70% (RR: 3.19 95% C.I.: 1.185-8.502 p-value = 0.0245). Vaccination of infected-healthy animals with an anti-Leishmania vaccine significantly reduced clinical progression and decreased all-cause mortality. Use of vaccination in infected-healthy dogs can be a tool for Leishmania control.

Frequent Exposure to Many Hunting Dogs Significantly Increases Tick Exposure.

Certain professionals have more exposure to animals and therefore an increased risk of zoonoses. Professional hunting dog caretakers work with upwards of 50 dogs and are exposed to zoonoses through exposure to multiple potentially infectious canine secretions or excretions, as well as to the ticks that dogs carry. Dog caretakers reported having found embedded ticks on their bodies 5.83 times more than environment-only controls. Zoonotic Lyme disease, first in the United States for morbidity due to a vector-borne infection, has dramatically expanded its geographic range over the last two decades. This finding emphasizes the increased risk of tick-borne diseases, including Lyme disease, based on dog exposure and in areas of disease emergence.

Safety Analysis of Leishmania Vaccine Used in a Randomized Canine Vaccine/Immunotherapy Trial.

In Leishmania infantum-endemic countries, controlling infection within dogs, the domestic reservoir, is critical to public health. There is a need for safe vaccines that prevent canine progression with disease and transmission to others. Protective vaccination against Leishmania requires mounting a strong, inflammatory, Type 1 response. Three commercially available canine vaccines on the global veterinary market use saponin or inflammatory antigen components (Letifend) as a strong pro-inflammatory adjuvant. There is very little information detailing safety of saponin as an adjuvant in field trials. Safety analyses for the use of vaccine as an immunotherapeutic in asymptomatically infected animals are completely lacking. Leishmania infantum, the causative agent of canine leishmaniasis, is enzootic within U.S. hunting hounds. We assessed the safety of LeishTec® after use in dogs from two different clinical states: 1) without clinical signs and tested negative on polymerase chain reaction and serology or 2) without clinical signs and positive for at least one Leishmania diagnostic test. Vaccine safety was assessed after all three vaccinations to quantify the number and severity of adverse events. Vaccinated animals had an adverse event rate of 3.09%, whereas placebo animals had 0.68%. Receiving vaccine was correlated with the occurrence of mild, site-specific, reactions. Occurrence of severe adverse events was not associated with having received vaccine. Infected, asymptomatic animals did not have a higher rate of adverse events. Use of vaccination is, therefore, likely to be safe in infected, asymptomatic animals.

Semi-quantitative measurement of asymptomatic L. infantum infection and symptomatic visceral leishmaniasis in dogs using Dual-Path Platform® CVL.

Infection with Leishmania causes diseases with variable presentation. The most severe form is visceral leishmaniasis (VL), caused by either L. donovani or L. infantum. Despite efforts to eliminate VL, to date, molecular detection in resource-poor settings have lacked the accuracy and rapidity that would enable widespread field use and the need for accurate, sensitive assays to detect asymptomatic Leishmania infection has become apparent. The domestic dog serves as the primary reservoir host of L. infantum. Study of this reservoir population provides an opportunity to evaluate the sensitivity and specificity of diagnostics for well-defined, symptomatic, canine visceral leishmaniasis (CVL) and asymptomatic L. infantum infection. Blood samples from an L. infantum-endemic population of US hunting dogs were evaluated with Dual-Path Platform (DPP®) CVL compared to those obtained via direct detection methods (culture- and Leishmania-specific quantitative polymerase chain reaction, qPCR) and immunofluorescence anti-Leishmania antibody test (IFAT). Statistically significant correlations were found between DPP® CVL development time and clinical status, culture status, circulating DNA levels, and IFAT titer. DPP® CVL results correlated with both clinical severity of disease and serological evidence of asymptomatic L. infantum infection. By precisely documenting the minimum time required for the development of a clear positive result in DPP® CVL, this test could be used in a rapid, semi-quantitative manner for the evaluation of asymptomatic and symptomatic CVL. Our results also indicate that a similar test could be used to improve our understanding of human VL.

Telephone survey to investigate relationships between onychectomy or onychectomy technique and house soiling in cats.

OBJECTIVE To determine whether associations existed between onychectomy or onychectomy technique and house soiling in cats. DESIGN Cross-sectional study. SAMPLE 281 owners of 455 cats in Polk County, Iowa, identified via a list of randomly selected residential phone numbers of cat owners in that region. PROCEDURES A telephone survey was conducted to collect information from cat owners on factors hypothesized a priori to be associated with house soiling, including cat sex, reproductive status, medical history, and onychectomy history. When cats that had undergone onychectomy were identified, data were collected regarding the cat's age at the time of the procedure and whether a carbon dioxide laser (CDL) had been used. Information on history of house soiling behavior (urinating or defecating outside the litter box) was also collected. RESULTS Onychectomy technique was identified as a risk factor for house soiling. Cats for which a non-CDL technique was used had a higher risk of house soiling than cats for which the CDL technique was used. Cats that had undergone onychectomy and that lived in a multicat (3 to 5 cats) household were more than 3 times as likely to have house soiled as were single-housed cats with intact claws. CONCLUSIONS AND CLINICAL RELEVANCE Results of this cross-sectional study suggested that use of the CDL technique for onychectomy could decrease the risk of house soiling by cats relative to the risk associated with other techniques. This and other findings can be used to inform the decisions of owners and veterinarians when considering elective onychectomy for cats.