Prospective Study on the Incidence and Progression of Clinical Signs in Naïve Dogs Naturally Infected by Leishmania infantum

Abstract

The incidence of clinical and clinicopathological signs associated with the progression of infection was evaluated prospectively in 329 naïve young dogs exposed to Leishmania infantum transmission and examined periodically during 22 months (M). The dogs were part of Leishmania vaccine investigations performed under natural conditions. Vaccinated groups were considered in the evaluation when the vaccine resulted non-protective and the appearance and progression of signs did not differ statistically from controls at each time point, otherwise only control groups were included. 115 beagles were part of 3 studies (A to C) performed in the same kennel; 214 owned dogs (29 breeds, 2.3% beagles) were included in a study (D) performed in 45 endemic sites. At M22 the prevalence of any Leishmania infection stage classified as subpatent, active asymptomatic, or symptomatic was 59.8% in studies A–C and 29.2% in study D. Despite different breed composition and infection incidence, the relative proportion of active infections and the progression and type of clinical and clinicopathological signs have been similar in both study sets. All asymptomatic active infections recorded have invariably progressed to full-blown disease, resulting in 56 sick dogs at M22. In these dogs, lymph nodes enlargement and weight loss — recorded from M12 — were the most common signs. Cutaneous signs were seen late (M18) and less frequently. Ocular signs appeared even later, being sporadically recorded at M22. Most clinicopathological alterations became evident from M12, although a few cases of thrombocytopenia or mild non-regenerative anemia were already observed at M6. Albumin/globulin inversions were recorded from M12 and urea/creatinine increase appeared mostly from M18. Altogether our findings indicate that any susceptible young dogs naturally infected by L. infantum present a common pattern of progression of signs during 2 years post infection, providing clues for medical and epidemiological applied aspects.

Author Summary

Despite dogs representing the main reservoir for the most widespread entity of human leishmaniasis (zoonotic visceral leishmaniasis caused by Leishmania infantum, endemic in five continents), many aspects of canine leishmaniasis (CanL) are still poorly understood. Dog responses to the infection are complex and broadly follow the two patterns of substantial resistance or clinical susceptibility. The latter is a progressive condition eventually leading to a dog's death, being associated with an increasing infectiousness to phlebotomine vectors. Because most information on CanL comes from cross-sectional investigations such as in-clinic pet diagnosis or mass population surveys, knowledge on the individual natural course of the infection/disease is limited. Prospective investigations are rarely performed because they are difficult and expensive. We took advantage of 4 prospective studies on experimental Leishmania vaccines to investigate the time-course of clinical signs in susceptible young dogs exposed to natural infection. We found that, whatever the dog breed and the local incidence of leishmaniasis, any asymptomatic active infections detected in naïve animals invariably progress to full-blown disease, showing a common pattern of early and late signs during 2 years post infection. These findings may provide clues for medical and epidemiological applied aspects.