Comorbid infections induce progression of visceral leishmaniasis

Abstract

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.

Keywords: Canine leishmaniosis; Progression; Risk-factor; Tick-borne diseases.

Fig. 1

Distribution of Leishmania and tick-borne diseases in Brazilian dogs. a Distribution of tick-borne diseases and Leishmania seropositivity in full cross-sectional study cohort. Overall 82.96% of dogs were seropositive for one or more vector borne disease. b Tick-borne disease serostatus of dogs that tested positive via either ELISA and/or DPP® CVL for Leishmania. c Tick-borne disease serostatus of dogs that were negative via ELISA and DPP® CVL for Leishmania spp.

Fig. 2

Distribution of tick-borne diseases based on CanL clinical status or mortality. Tick-borne disease exposure determined as positive or negative via ELISA. Leishmania spp. determined as diagnostically positive via qPCR and/or DPP® CVL. a Dogs with clinical leishmaniosis determined as dogs with three or more clinical signs of leishmaniosis and diagnostically positive for Leishmania via qPCR and/or DPP® CVL. b All-cause mortality determined as death for any reason