Leukocytes and Albumin in Canine Leishmaniasis


  • Társsila Mara Vieira Ferreira Programa de Pós-Graduação em Ciências Veterinárias, Faculdade de Veterinária, Universidade Estadual do Ceará (UECE), Fortaleza, CE, Brazil.
  • Alexandre Tavares Camelo Oliveira Programa de Pós-Graduação em Ciências Veterinárias, Faculdade de Veterinária, Universidade Estadual do Ceará (UECE), Fortaleza, CE, Brazil.
  • Victor Machado de Carvalho Programa de Pós-Graduação em Ciências Veterinárias, Faculdade de Veterinária, Universidade Estadual do Ceará (UECE), Fortaleza, CE, Brazil.
  • Ana Débora Nunes Pinheiro Programa de Pós-Graduação em Ciências Veterinárias, Faculdade de Veterinária, Universidade Estadual do Ceará (UECE), Fortaleza, CE, Brazil.
  • Thaíse Cristine Ferreira de Carvalho Sombra Programa de Pós-Graduação em Ciências Veterinárias, Faculdade de Veterinária, Universidade Estadual do Ceará (UECE), Fortaleza, CE, Brazil.
  • Tiago Cunha Ferreira Programa de Pós-Graduação em Ciências Veterinárias, Faculdade de Veterinária, Universidade Estadual do Ceará (UECE), Fortaleza, CE, Brazil. https://orcid.org/0000-0002-0130-022X
  • José Cláudio Carneiro de Freitas Programa de Pós-Graduação em Ciências Veterinárias, Faculdade de Veterinária, Universidade Estadual do Ceará (UECE), Fortaleza, CE, Brazil.
  • Diana Célia Sousa Nunes-Pinheiro Programa de Pós-Graduação em Ciências Veterinárias, Faculdade de Veterinária, Universidade Estadual do Ceará (UECE), Fortaleza, CE, Brazil.




Background: Canine Leishmaniasis (CanL) is a multisystemic and chronic inflammatory disease characterized by nonspecific clinical manifestations. In CanL, inflammatory cells and chemical mediators released in response to the parasite play a role in disease development and progression. Alterations on hematological parameters have been documented in CanL. These changes can also be assessed in relation to systemic inflammation caused by this disease. The circulating leukocyte counting, such as neutrophils, as well as the albumin level, are considered direct indicators of an inflammatory host environment. Several studies point to the use of biomarkers on the assistance in diagnosis and prognosis of several canine pathologies. The present study investigated the Neutrophils to Lymphocyte Ratio (NLR), Albumin to Globulin Ratio (AGR), and Neutrophils to Albumin Ratio (NAR) on systemic inflammatory response induced by Canine Leishmaniasis (CanL).

Materials, Methods & Results: For this purpose, adult dogs with confirmed diagnosis to CanL were divided into symptomatic (SD, n = 33) and asymptomatic (AD, n = 20) dogs for L. infantum and control dogs (CD, n = 20). Routine hematological and biochemical parameters were determined in blood samples using a veterinary automatic hematology and biochemical analyzers. Asymptomatic dogs (AD) had a higher number of white blood cells and neutrophils (16.48 ± 4.93; 13.41 ± 3.60, respectively) in relation to symptomatic dogs (SD) (13.54 ± 5.13; 10.42± 3.69, respectively) (P = 0.015 and P < 0.0001, respectively). Neutrophils to Lymphocyte Ratio (NLR) was higher in dogs with leishmaniasis (9.45 ± 3.76) than in healthy dogs (3.39 ± 1.19) (P < 0.0001). Serum total proteins (STP) and globulins increased in CanL, while albumin and AGR decreased in CanL, when compared to CD and references values to canine species. Neutrophils to Albumin Ratio (NAR) was higher in AD and SD (5.02 ± 1.14; 4.79 ± 1.07, respectively) when compared to CD (2.36 ± 0.55) (P < 0.0001).

Discussion: As reported in scientific researches, dogs with Leishmaniasis present alterations in circulating cell counts. Based on these data, we decided to expand this information using the NLR as a parameter in an attempt to better clarify the changes in these cells in CanL. We observed that NLR was increased on CanL in relation to healthy dogs, which could be a consequence of relative neutrophilia rather than lymphopenia. Neutrophils to Lymphocyte Ratio (NLR) is a biomarker that conveys information about inflammatory conditions. An elevated NLR can reflect an upregulated innate immune response, since neutrophils are effector cells of innate immunity and are involved in several acute and chronic inflammatory processes. Albumin is an acute phase protein that is considered an immune-inflammatory biomarker, which can be found reduced systemically in progressive inflammatory response. Serum total proteins (STP) and globulins were increased in CanL. These data are already well documented in CanL, which serum globulins are mainly associated with the increase of acute phase proteins, cytokines, and increase of specific antibodies to Leishmaniainfantum. Our results showed neutrophilia with hypoalbuminemia in CanL. So, in an attempt to assess the relationship of these two available markers, we used NAR calculation in order to evaluate the changes induced by CanL. In this study NAR was higher in CanL when compared to control dogs. Thus, our data indicate that NLR and NAR could be used as biomarkers in veterinary medical clinics in order to assess inflammatory profile in CanL, mainly in asymptomatic dogs. These parameters obtained from routine blood tests might be useful as cost-effective, easily accessible and helpful markers in order to distinguish the inflammatory response intensity in CanL.


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Abbehusen M.M.C., Almeida V.D.A., Solcà M.D.S., Pereira L.S., Costa D.J., Gil-Santana L., Bozza P.T., Fraga D.B.M., Veras P.S.T., Santos W.L.C., Andrade B.B. & Brondskyn C.I. 2017. Clinical and immunopathological findings during long term follow-up in Leishmania infantum experimentally infected dogs. Scientific Reports. 7(1): 15914.

Almeida B.F.M., Narciso L.G., Melo L.M., Preve P.P., Bosco A.M., Lima V.M.F. & Ciarlini P.C. 2013. Leishmaniasis causes oxidative stress and alteration of oxidative metabolism and viability of neutrophils in dogs. The Veterinary Journal. 198(3): 599-605.

An I., Ayhan E., Aksoy M., Erat T. & Doni N.Y. 2021. Evaluation of inflammatory parameters in patients with cutaneous leishmaniasis. Dermatologic Therapy. 34(1): e14603.

Artigas A., Wernerman J., Arroyo V., Vincent J.L. & Levy M. 2016. Role of albumin in diseases associated with severe systemic inflammation: pathophysiologic and clinical evidence in sepsis and in decompensated cirrhosis. Journal of Critical Care. 33: 62-70.

Cantos-Barreda A., Escribano D., Martínez-Subiela S., Pardo-Marin L., Segarra S. & Céron J.J. 2018. Changes in serum anti-Leishmania antibody concentrations measured by time-resolved immunofluorometric assays in dogs with leishmaniosis after treatment. Veterinary Immunology and Immunopathology. 198: 65-69.

Cascao R., Rosario H.S. & Fonseca J.E. 2009. Neutrophils: warriors and commanders in immune mediated inflammatory diseases. Acta Reumatológica Portuguesa. 34(2B): 313-326.

Chagas A.C., Oliveira F., Debrabant A., Valenzuela J.G., Ribeiro J.M.C. & Calvo E. 2014. Lundep, a sand fly salivary endonuclease increases Leishmania parasite survival in neutrophils and inhibits xiia contact activation in human plasma. PLoS Pathogens. 10(2): e1003923.

Cui H., Ding X., Li W., Chen H. & Li H. 2019. The neutrophil percentage to albumin ratio as a new predictor of in-hospital mortality in patients with st-segment elevation myocardial infarction. Medical Science Monitor. 25: 7845-7852.

Freitas J.C.C., Nunes-Pinheiro D.C.S., Lopes Neto B.E., Santos G.J.L., Abreu C.R.A., Braga R.R., Campos R.M. & de Oliveira L.F. 2012. Clinical and laboratory alterations in dogs naturally infected by Leishmania chagasi. Revista da Sociedade Brasileira de Medicina Tropical. 45(1): 24:29.

Freeman P.K. & Klenner S. 2015. Veterinary clinical pathology. A case-based approach. Boca Raton: CRS Press, 288p.

Gabriel C., McMaster W.R., Girard D. & Descoteaux A. 2014. Leishmania donovani promastigotes evade the antimicrobial activity of neutrophil extracellular traps. Journal of Immunology. 185(7): 4319-4327.

Gong Y., Li D., Cheng B., Ying B. & Wang B. 2020. Increased neutrophil percentage-to-albumin ratio is associated with all-cause mortality in patients with severe sepsis or septic shock. Epidemiology and Infection. 148: e8.

Gradel K.O., Vinholt P.J., Magnussen B., Pedersen C., Jensen T.G., Kolmos H.J. & Lassen A.T. 2018. Hypoalbuminaemia as a marker of trans-capillary leakage in community-acquired bacteraemia patients. Epidemiology and Infection. 146(5): 648-655.

Guimarães-Costa A.B., Nascimento M.T.C., Froment G.S., Soares R.P.P., Morgado F.N., Conceição-Silva F. & Saraiva E.M. 2009. Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps. Proceedings National Academy of Sciences. 106(16): 6748-6753.

Guthrie G.J., Charles K.A., Roxburgh C.S.D., Horgan P.G., McMillan D.C. & Clarke S.J. 2013. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Critical Review in Oncology/Hematology. 88(1): 218-30.

Ha C.E. & Bhagavan N.V. 2013. Novel insights into the pleiotropic effects of human serum albumin in health and disease. Biochimica et Biophysica Acta. 1830(12): 5486-5493.

Hodgson N., Llewellyn E.A. & Schaeffer D.J. 2018. Utility and prognostic significance of neutrophil-to-lymphocyte ratio in dogs with septic peritonitis. Journal of the American Animal Hospital Association. 54(6): 351-359.

Hsu B.E., Shen Y. & Siegel P.M. 2020. Neutrophils: orchestrators of the malignant phenotype. Frontiers in Immunology. 11: 1778.

Hurrell B.P., Regli I.B. & Tacchini-Cottier F. 2016. Different Leishmania species drive distinct neutrophil functions. Trends in Parasitology. 32(5): 392-401.

Kinoshita H., Watanabe K., Azma T., Feng G.G., Akahori T., Hayashi H., Sato M., Fujiwara Y. & Wakatsuki A. 2017. Human serum albumin and oxidative stress in preeclamptic women and the mechanism of albumin for stress reduction. Heliyon. 3(8): e00369.

Laurenti M.D., Rossi C.N., da Matta V.L.R., Tomokane T.Y., Corbett C.E.P., Secundino N.F.C., Pimenta P.F.P. & Marcondes M. 2013. Asymptomatic dogs are highly competent to transmit Leishmania (Leishmania) infantum chagasi to the natural vector. Veterinary Parasitology. 196(3-4): 296-300.

Leal G.G.A., Roatt B.M., Aguiar-Soares R.D.O., Carneiro C.M., Giunchetti R.C., Teixeira-Carvalho A., Martins Filho O.A., Francisco A.F., Cardoso J.M., Mathias F.A.S., Correa-Oliveira R., Carneiro M., Coura-Vital W. & Reis A.B. 2014. Immunological profile of resistance and susceptibility in naturally infected dogs by Leishmania infantum. Veterinary Parasitology. 205(3-4): 472-482.

Liew P.X. & Kubes P. 2019. The neutrophil’s role during health and disease. Physiological Reviews. 99(2): 1223-1248.

Macfarlane L., Morris J., Pratschke K., Mellor D., Scase T., Macfarlane M. & Mclauchlan G. 2015. Diagnostic value of neutrophil-lymphocyte and albumin-globulin ratios in canine soft tissue sarcoma. Journal of Small Animal Practice. 57(3): 135-141.

Macfarlane M.J., Macfarlane L.L., Scase T., Parkin T. & Morris J.S. 2016. Use of neutrophil to lymphocyte ratio for predicting histopathological grade of canine mast cell tumours. Veterinary Records. 179(19): 1-6.

Martin H.L., Ohara K., Kiberu A., Hagen T.V., Davidson A. & Khattak M.A. 2014. Prognostic value of systemic inflammation-based markers in advanced pancreatic cancer. Internal Medicine Journal. 44(7): 676-682.

Martínez-Orellana P., Marí-Martorell D., Montserrat-Sangrà S., Ordeix L., Baneth G. & Solano-Gallego L. 2017. Leishmania infantum-specific IFN-γ production in stimulated blood from dogs with clinical leishmaniosis at diagnosis and during treatment. Veterinary Parasitology. 248: 39-47.

Mutz M., Boudreaux B., Kearney M., Stroda K., Gaunt S. & Shiomitsu K. 2013. Prognostic value of baseline absolute lymphocyte concentration and neutrophil/lymphocyte ratio in dogs with newly diagnosed multi-centric lymphoma. Veterinary and Comparative Oncology. 13(4): 337-347.

Norberg Å., Rooyackers O., Segersvärd R. & Wernerman J. 2015. Albumin kinetics in patients undergoing major abdominal surgery. PLoS One. 10(8): e0136371.

Oikonomidis I.L., Tsouloufi T.K., Mylonakis M.E., Psalla D., Soubasis N., Rallis T. & Kritsepi-Konstantinou M. 2019. Circulating and bone marrow myeloid cells containing Leishmania amastigotes in a case of advanced canine leishmaniosis. Journal of Veterinary of Diagnostic Investigation. 31(5): 726-731.

Oualha R., Barhoumi M., Marzouki S., Harigua-Souiai E., Ahmed M.B. & Guizani I. 2019. Infection of human neutrophils with Leishmania infantum or Leishmania major strains triggers activation and differential cytokines release frontier in cellular and infection. Microbiology. 9: 153.

Peters N.C., Egen J.G., Secundino N., Debrabant A., Kimblin N., Kamhawi S., Lawyer P., Fay M.P., Germain R.N. & Sacks D. 2008. In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies. Science. 321(5891): 970-974.

Pereira M.A., Alexandre-Pires G., Câmara M., Santos M., Martins C., Rodrigues A., Adriana J., Passero L.F.D., Da Fonseca I.P. & Santos-Gomes G. 2019. Canine neutrophils cooperate with macrophages in the early stages of Leishmania infantum in vitro infection. Parasite Immunology. 41(4): e12617.

Pierini A., Gori E., Lippi I., Ceccherini G., Lubas G. & Marchetti V. 2019. Neutrophil-to-lymphocyte ratio, nucleated red blood cells and erythrocyte abnormalities in canine systemic inflammatory response syndrome. Research in Veterinary Science. 126: 150-154.

Qu J., Yuan H.-Y., Huang Y., Qu Q., Ou-Yang Z.-B., Li G.-H., Zhu H.-H. & Lu Q. 2019. Evaluation of neutrophil-lymphocyte ratio in predicting bloodstream infection. Biomarkers in Medicine. 13(15): 1255-1261.

Reis A.B., Martins Filho O.A., Teixeira-Carvalho A., Carvalho M.G., Mayrink W., França-Silva J.C., Giunchetti R.C., Genaro O. & Corrêa-Oliveira R. 2006. Parasite density and impaired biochemical/hematological status are associated with severe clinical aspects of canine visceral leishmaniasis. Research in Veterinary Science. 81(1): 68-75.

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. Veterinary Immunology and Immunopathology. 128(1-3): 87-95.

Ribeiro R.R., Silva S.M., Fulgêncio G.O., Michalick M.S.M. & Frézard F.J.G. 2013. Relationship between clinical and pathological signs and severity of canine leishmaniasis. Revista Brasileira de Parasitologia Veterinária. 22(3): 373-378.

Ribeiro-Gomes F.L. & Sacks D. 2012. The influence of early neutrophil-Leishmania interactions on the host immune response to infection. Frontiers in Cellular and Infection Microbiology. 2: 59.

Roche M., Rondeau P., Singh N.R., Tarnus E. & Bourdon E. 2008. The antioxidant properties of serum albumin. Febs Letters. 582(13): 1783-1787.

Rosales C. 2020. Neutrophils at the crossroads of innate and adaptive immunity. Journal of Leukcyte Biology. 108(1): 377-396.

Rossaint J., Margraf A. & Zarbock A. 2018. Role of platelets in leukocyte recruitment and resolution of inflammation. Frontiers in Immunology. 9: 1-13.

Roura X., Cortadellas O., Day M.J., Benali S.L., Group C.L.W. & Zatelli A. 2020. Canine leishmaniosis and kidney disease: Q&A for an overall management in clinical practice. Journal of Small and Animal Practice. 62(1): E1-E19.

Sadik C.D., Kim N.D. & Luster A.D. 2011. Neutrophils cascading their way to inflammation. Trends in Immunology. 32(10): 452-460.

Solano-Gallego L., Koutinas A., Miró G., Cardoso L. & Pennisi M.G. 2009. Directions for the diagnosis, clinical staging, treatment and prevention of canine leishmaniasis. Veterinary Parasitology. 165(1-2): 1-18.

Verçosa B.L.A., Muniz-Junqueira M.I., Menezes-Souza D., Fujiwara R.T., Melo M.N. & Vasconcelos A.C. 2021. The balance between IL-12/IL4 in renal tissue switches the inflammatory response arm and shows relationship with the clinical signs in Leishmania-infected dogs. Veterinary Immunology and Immunopathology. 234: 110196.

Wang B., Li D., Cheng B., Ying B. & Gong Y. 2020. The neutrophil percentage-to-albumin ratio is associated with all-cause mortality in critically ill patients with acute kidney injury. BioMed Research International. 18: 5687672.



How to Cite

Ferreira, T. M. V., Oliveira, A. T. C., de Carvalho, V. M., Pinheiro, A. D. N., de Carvalho Sombra, T. C. F., Ferreira, T. C., de Freitas, J. C. C., & Nunes-Pinheiro, D. C. S. (2021). Leukocytes and Albumin in Canine Leishmaniasis. Acta Scientiae Veterinariae, 49. https://doi.org/10.22456/1679-9216.111869




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