Aspectos clínicos, falha de tratamento e recidivas na Leishmaniose Visceral: uma abordagem bibliográfica e experimental para relacionar esses fatores com a tolerância medicamentosa de isolados clínicos de Leishmania infantum

Abstract

Leishmaniasis is a group of neglected diseases that affect many underdeveloped or developing countries. The main clinical presentations of the disease are the visceral and tegumentary forms, caused by parasites of the Leishmania genus, which includes more than 20 species that cause the disease. The use of drugs is the main method used for the control and treatment of diseases, however, this methodology encounters obstacles, given the limited amount of drugs available on the market, in addition to problems frequently addressed in the literature, such as the possibility of the presence of resistant parasites and the occurrence of Treatment Failures and Clinical Relapses as factors that hinder a favorable clinical outcome. In this sense, this work proposed in Chapter I a literature review that understood the processes involved in the cases of Treatment Failures (TF) and Clinical Relapses (CR) in the two clinical presentations of Leishmaniasis in the world. The methodology was based on obtaining scientific articles published in databases between 1990 and 2021 in Portuguese, English and Spanish relating cases of Cutaneous Leishmaniasis (CL) and Visceral Leishmaniasis (VL) in humans with FT and CR, including both epidemiological and experimental studies. In the results achieved, it is possible to observe that TF and RC are multifactorial, with a set of conditions that mainly involves the plastic ability of the parasite to resist and evade the action of drugs and factors related to the immunological competence of the host, being the clinical picture of TF and CR arising from this combination or the presentation of these isolated circumstances. In Chapter II, a correlation was performed between clinical/laboratory data from patients with Visceral Leishmaniasis and the sensitivity of clinical isolates of Leishmania (Leishmania) infantum against Trivalent Antimony and Amphotericin B. The method used is based on the collection and cultivation of parasites obtained from clinical isolates, in vitro sensitivity assays of the promastigote forms against Trivalent Antimony and Amphotericin B to obtain the EC50 and correlation analysis of the clinical variables of the patients with the experimental data. The EC50 of the collected clinical isolates was obtained, compared with the result of the standard strain, classified as susceptible or resistant and correlated with the clinical and laboratory findings of the patients. A positive association was not found between the presence of the resistant parasite and the involvement with more severe clinical signs and symptoms and/or the occurrences of TF or CR, however, a relationship was observed between the presence of immunosuppressive diseases and CR cases. In addition, we also found a direct correlation between the sensitivity of the parasite to both drugs, thus indicating that there is a tendency towards cross-resistance between the clinical isolates analyzed. Thus, experimental trials indicate that for Leishmania (L.) infantum, the parasite's sensitivity to drugs does not seem to be the most direct cause for the clinical outcome of TF or CR, reinforcing the findings of the literature review that point to these phenomena as complex multifactorial processes, which involve both aspects of the parasite (not only in vitro sensitivity) and the host response.