Veterinary Parasitology 202 (2014) 341–342

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Letter to the Editor When is an “asymptomatic” dog asymptomatic? To the Editor, We read with interest the paper entitled “Asymptomatic dogs are highly competent to transmit Leishmania (Leishmania) infantum chagasi to the natural vector” by Laurenti and colleagues (2013), which was recently published in Veterinary Parasitology. The research reported in the paper addressed a quite important issue, which is the infectiousness of dogs infected by Leishmania infantum (=Leishmania infantum chagasi) to phlebotomine sand flies. The authors concluded that “asymptomatic dogs are highly infective and competent for establishing sand fly infection, indicating their role in maintaining L. (L.) infantum chagasi cycle as well as their involvement in visceral leishmaniasis (VL) spreading in endemic areas”. But the question is: When is an “asymptomatic” dog asymptomatic? From a clinical perspective, dogs should be classified as “infected by L. infantum but healthy” or as “sick” (Solano-Gallego et al., 2011). Indeed, clinically healthy but infected dogs are those with no clinical signs upon physical examination or clinical pathological abnormalities (e.g., complete blood count, biochemical profile and urinalysis) but with confirmed L. infantum infection (Solano-Gallego et al., 2011). On the other hand, sick dogs are those presenting clinical signs (e.g., lymph node enlargement, loss of body weight, lethargy, and skin lesions) and/or clinical pathological abnormalities (e.g., hypoalbuminemia, decreased albumin/globulin ratio, and thrombocytopenia) and with confirmed L. infantum infection. Definitely, dogs with enlarged lymph nodes must be regarded as sick (Solano-Gallego et al., 2011). Conversely, in the study by Laurenti et al. (2013), 50% of the dogs classified as “asymptomatic” presented mild popliteal lymph node enlargement, which means that they were sick with mild disease (or “Stage I”), according to the LeishVet group’s classification (Solano-Gallego et al., 2011). Laurenti et al. (2013) found no statistically significant differences in the parasite load in skin, lymph nodes and spleen between “asymptomatic” and symptomatic dogs, but animals from the latter group presented more parasites in the skin. Likewise, symptomatic dogs presented significantly higher anti-Leishmania

http://dx.doi.org/10.1016/j.vetpar.2014.02.008 0304-4017/© 2014 Elsevier B.V. All rights reserved.

antibodies titres as measured by ELISA (Laurenti et al., 2013). It is well established in the international literature that infected but clinically healthy dogs are usually seronegative or present medium antibody levels, cellular response to Leishmania antigens, and may be PCR negative or positive. On the other hand, sick dogs usually display high antibody levels, depressed cell-mediated immune response and are usually PCR positive (Solano-Gallego et al., 2009). Remarkably, there is an inverse correlation between the CD4+ T-cell count in naturally infected dogs and their infectiousness to phlebotomine sand flies (Guarga et al., 2000). Indeed, the lower the CD4+ T-cell count in the dog, the higher the rate of the infection in the vector. Accordingly, infected but healthy dogs usually present normal CD4+ T-cell counts, whereas sick dogs present decreased CD4+ T-cell levels (Reis et al., 2009). While the term “asymptomatic” is still used in the international literature, it is falling into disuse. Indeed, the classification of dogs as asymptomatic, oligosymptomatic and polysymptomatic based only on physical examination (Mancianti et al., 1988) is of limited value, because it does not consider clinical pathological abnormalities and also disregards dogs presenting organ dysfunction but without apparent clinical manifestations (Solano-Gallego and Baneth, 2008). Therefore, we recommend all authors dealing with canine VL to adhere to the LeishVet guidelines (Solano-Gallego et al., 2009, 2011), which is a wellbalanced consensus on several aspects of the disease, carefully prepared by a group of renowned specialists in the field. Although we really appreciate the efforts made by Laurenti and colleagues in studying such an important issue, it is clear to us that these methodological drawbacks invalidate the conclusions of their investigation. Indeed, due to a misclassification of dogs according to the clinical stages, asymptomatic dogs were regarded as “highly infective” to phlebotomine sand flies. This unintentional mistake may result in the unnecessary elimination of millions of dogs in some countries, like Brazil, where the dog culling strategy is still used to control visceral leishmaniasis (Dantas-Torres and Otranto, 2014), in spite of the availability of more humane and scientifically sound measures, such as vaccines and repellents (Solano-Gallego et al., 2009, 2011; Dantas-Torres et al., 2012; reviewed in Otranto and DantasTorres, 2013).

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Letter to the Editor / Veterinary Parasitology 202 (2014) 341–342

Conflict of interest statement The authors declare there are no conflicts of interest. References Dantas-Torres, F., Otranto, D., 2014. Dogs, cats, parasites, and humans in Brazil: opening the black box. Parasit. Vectors 7, 22. Dantas-Torres, F., Solano-Gallego, L., Baneth, G., Ribeiro, V.M., de PaivaCavalcanti, M., Otranto, D., 2012. Canine leishmaniosis in the Old and New Worlds: unveiled similarities and differences. Trends Parasitol. 28, 531–538. ˜ Guarga, J.L., Moreno, J., Lucientes, J., Gracia, M.J., Peribánez, M.A., Alvar, J., Castillo, J.A., 2000. Canine leishmaniasis transmission: higher infectivity amongst naturally infected dogs to sand flies is associated with lower proportions of T helper cells. Res. Vet. Sci. 69, 249–253. Laurenti, M.D., Rossi, C.N., da Matta, V.L., Tomokane, T.Y., Corbett, C.E., Secundino, N.F., Pimenta, P.F., Marcondes, M., 2013. Asymptomatic dogs are highly competent to transmit Leishmania (Leishmania) infantum chagasi to the natural vector. Vet. Parasitol. 196, 296–300. Mancianti, F., Gramiccia, M., Gradoni, L., Pieri, S., 1988. Studies on canine leishmaniasis control. 1. Evolution of infection of different clinical forms of canine leishmaniasis following antimonial treatment. Trans. R. Soc. Trop. Med. Hyg. 82, 566–567. Otranto, D., Dantas-Torres, F., 2013. The prevention of canine leishmaniasis and its impact on public health. Trends Parasitol. 29, 339–345. Reis, A.B., Martins-Filho, O.A., Teixeira-Carvalho, A., Giunchetti, R.C., Carneiro, C.M., Mayrink, W., Tafuri, W.L., Corrêa-Oliveira, R., 2009. Systemic and compartmentalized immune response in canine visceral leishmaniasis. Vet. Immunol. Immunopathol. 128, 87–95. Solano-Gallego, L., Baneth, G., 2008. Canine leishmaniosis – a challenging zoonosis. Eur. J. Comp. Anim. Pract. 18, 232–241. Solano-Gallego, L., Koutinas, A., Miró, G., Cardoso, L., Pennisi, M.G., Ferrer, L., Bourdeau, P., Oliva, G., Baneth, G., 2009. Directions for the diagnosis,

clinical staging, treatment and prevention of canine leishmaniosis. Vet. Parasitol. 165, 1–18. Solano-Gallego, L., Miró, G., Koutinas, A., Cardoso, L., Pennisi, M.G., Ferrer, L., Bourdeau, P., Oliva, G., Baneth, G., The LeishVet Group, 2011. LeishVet guidelines for the practical management of canine leishmaniosis. Parasit. Vectors 4, 86.

Filipe Dantas-Torres a,b,∗ Department of Immunology, Aggeu Magalhães Research Centre, Oswaldo Cruz Foundation, Recife, Pernambuco 50670420, Brazil b Department of Veterinary Medicine, University of Bari, Valenzano, Bari 70010, Italy a

Domenico Otranto Department of Veterinary Medicine, University of Bari, Valenzano, Bari 70010, Italy ∗ Corresponding

author at: Department of Immunology, Aggeu Magalhães Research Centre, Oswaldo Cruz Foundation, Recife, Pernambuco 50670420, Brazil. Tel.: +55 81 21012551; fax: +55 81 21012640. E-mail address: fi[email protected] (F. Dantas-Torres) 18 December 2013 4 February 2014 8 February 2014

When is an "asymptomatic" dog asymptomatic?

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