Leishmaniose visceral: correlação entre os achados clínicos, laboratoriais e as características imunológicas do micro ambiente da medula óssea

Abstract

Leishmaniasis is an endemic disease of tropical and subtropical countries. It is associated with malnutrition, displacement of populations, poverty, immunodeficiencies and lack of financial resources. In Brazil, 53,442 cases of Visceral Leishmaniasis (VL) were reported between 2001 and 2016. The objective of this study was to correlate the clinical and laboratory findings, immuno-morphological characteristics and parasitic load of the bone marrow. The pathogenesis and severity of anemia associated with the findings were verified. Anemia was classified as severe Hb ≤ 7g / dL and not severe Hb> 7g / dL. The parasite load of the bone marrow was measured by optical microscopy and by the Quantitative Polymerase Chain Reaction (qPCR) technique. Interleukins (IL) were analyzed from the bone marrow by the qPCR technique. Children younger than 9 years of age accounted for the majority of individuals 15/19 (78.9%). Fever, hepatosplenomegaly and anemia were present in 100% of the individuals. Pancytopenia was observed in 13/19 (68.4%) of the participants. Severe anemia was observed in 8/19 (42.1%) and non-severe in 11/19 (57.9%). Serum erythropoietin (EPO) was elevated in 17/19 (89.5%) and with statistical significance between groups (p = 0.038) and a negative correlation with hemoglobin (p = 0.029, rho = -0.519). Anemia in the individuals analyzed was neither autoimmune nor hemolytic type autoimmune. The ultra sensitive C-Reactive Protein (CRP) showed significance (p = 0.047) between the groups. Liver size had a significant positive correlation with Glutamic Oxalacetic Transaminase (OLT) (p = 0.054, rho = 0.490), Activated Partial Thromboplastin Time (APTT) (p = 0.005, rho = 0.648) and parasite load by qPCR (p = 0.040, rho = 0.502). Lactate dehydrogenase (LDH) was elevated in 17/19 (89.5%) with a significant positive correlation with ORT (p = 0.000, rho = 0.805), International Normative Relationship (INR) (p = 0.007, rho = 0.625) , APTT (p = 0.008, rho = 0.621) and erythrocyte series (p = 0.005, rho = 0.648). The RNI showed a significant positive correlation with CRP (p = 0.024, rho = 0.544). The colony stimulating factor 2 (CSF-2) presented statistical significance between the groups (p = 0.036) and a tendency to a negative correlation with hemoglobin (p = 0.590, rho = -0.481) and a positive correlation with EPO (p = 0.009, rho = 0.647). There is a positive correlation between Interferon Gamma (IFN-γ) and liver size (p = 0.009, rho = 0.651), Interleukin-6 (IL 6) (p = 0.000, rho = 0.907), Interleukin-10 IL-10) (p = 0.000, rho = 0.778) and tumor necrosis factor alpha (TNF-α) (p = 0.028, rho = 0.549) and a correlation of TNF-α with IL-6 (p = 0.008, rho = 0.636) and IL-10 (p = 0.000, rho = 0.783). The evaluation of the bone marrow showed a low parasitic load, by light microscopy, in 14/19 (73.7%). There was a positive correlation between parasitic loads (p = 0.006, rho = 0.635). Cytological analysis revealed normocellular bone marrow in 14/19 (73.7%). The erythrocytic series presented with relative hyperplasia in 18/19 (94.7%) and dyseritropoietic 19/19 (100%). Knowledge of clinical and laboratory characteristics in VL may play an important role in the differential diagnosis of febrile hepatosplenomegaly, especially in endemic areas and in a developing country where resources are limited. It is important to evaluate the morphological characteristics of the bone marrow through aspiration as a tool that helps and guides the diagnosis of visceral leishmaniasis. From the results of the study, it is concluded that the anemia is not related to charac- teristic factors, blood loss and / or autoimmune hemolysis and that the hemoglobin levels in the individuals with active VL are correlated with the inflammatory response promoted by this pathology. The work is relevant to subsidize the development of new studies and may target immunotherapy-based therapies.