Canine Leishmaniasis Is a Risk Factor for Ehrlichia canis Infection

Canine leishmaniasis, carried by a phlebotomine sand fly, is caused by Leishmania infantum. It is endemic in such places as Central America and the Mediterranean. Other vector-borne pathogens (VBPs), such as Ehrlichia canis, are often present with canine leishmaniasis, making the clinical course unpredictable and worsening prognosis.

L infantum suppresses the immune system by stimulating the release of immunosuppressive substances. Whether leishmaniasis is a risk factor for coinfection with VBPs, though, has not yet been determined.

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In the first study of its kind, a research team tested the hypothesis that canine leishmaniasis increases the risk of VBP coinfections. The results, particularly that canine leishmaniasis markedly increases the risk of an E. canis coinfection, were recently reported in Parasites & Vectors.

Analysis

The researchers collected and analyzed blood samples from dogs naturally infected with L infantum (n = 50) and age-, breed-, and sex-matched clinically healthy dogs (controls, n = 92). The dogs lived in Paphos, Cyprus.

Polymerase chain reaction was performed to detect Leishmania spp, Babesia spp, Candidatus Mycoplasma haematoparvum (CMhp), Mycoplasma haemocanis, Ehrlichia/Anaplasma spp, and Hepatozoon spp. An enzyme-linked immunosorbent assay (ELISA) was also performed to detect L infantum antibodies.

Logistic regression analysis and structural equation modeling (SEM) were used to determine associations between canine leishmaniasis and the other VBPs. SEM, which is an advanced method of regression analysis, allowed for investigation of the “effects of demographics, lifestyle, and breed on VPB infection” in this study, the researchers wrote.

Results

The study dogs were primarily purebred and had a median age of 5.6 years. The following VBP detection frequencies for each study group were observed:

Canine leishmaniasis

• Hepatazoon spp: 48%
• Mycoplasma haemocanis: 28%
• Ehrlichia canis: 12%
• Anaplasma platys: 4%

Controls

• Hepatazoon spp: 45%
• M haemocanis: 20%
• E canis: 1%
• A platys: 3%

Babesia spp and CMhp were not detected in any samples.

Compared with control dogs, dogs with leishmaniasis were 12 times more likely to have an E canis coinfection. This finding suggests synergism between L infantum and E canis in dogs. Such synergism, compared with either infection alone, worsens hematologic changes and clinical outcome.

Notably, L infantum’s immunosuppressive activity could reactivate a latent E canis infection or facilitate a new one, the researchers noted. In addition, the ability of E canis to downregulate major histocompatibility complex class II, which regulates the immune response to L infantum, could influence the clinical outcome of a Leishmania infection.

In humans, Leishmania and HIV co-exist in macrophages and trigger a complex immune response. This synergism hastens progression to AIDS and increases the risk of visceral leishmaniasis. Given that L infantum and E canis infect monocytes and macrophages, it is possible that they also have complex immunopathologic mechanisms. More studies, the researchers noted, will be needed to investigate how L infantum and E canis coinfections affect the canine immune system.

Logistic regression analysis revealed no other statistically significant associations.

SEM analysis revealed that young dogs were at high risk of coinfections with Heptazoon spp and M haemocanis, suggesting that young dogs may have increased exposure to VBPs.

Clinical Implications

The association between canine leishmaniasis and E. canis ”could impact the diagnostic and monitoring management of canine leishmaniasis,” the researchers believed. Recommendations based on the study’s findings include performing PCR testing for E canis in dogs with leishmaniasis and, in the event of a coinfection, treating both infections simultaneously.

Dr. Pendergrass received her doctor of veterinary medicine degree from the Virginia-Maryland College of Veterinary Medicine. She then completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner of JPen Communications, a medical communications company.