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The present study aimed to evaluate the anti-staphylococcal, antibiofilm, cytotoxicity and trypanocidal activity, mechanisms of parasite death and immunomodulatory effect of CrataBL encapsulated into liposomes (CrataBL-Lipo). CrataBL-Lipo were prepared by the freeze-thaw technique and characterized. Anti-staphylococcal and antibiofilm activities of CrataBL and CrataBL-Lipo were evaluated against standard and clinical strains of Staphylococcus aureus susceptible and resistant. Thus, broth microdilution method was performed to determine the Minimum Inhibitory Concentration (MIC). Antibiofilm activity at subinhibitory concentrations was evaluated using the crystal violet staining method. Cytotoxicity of CrataBL-Lipo was verified in L929 fibroblasts and J774A.1 macrophages by determining the inhibitory concentration necessary to kill 50 % of cells (IC50). Trypanocidal activities of CrataBL-Lipo was evaluated in Trypanosoma cruzi and the efficacy was expressed as the concentration necessary to kill 50 % of parasites (EC50). The mechanisms of parasite death and immunomodulatory effect of CrataBL-Lipo were evaluated using flow cytometry analysis. CrataBL-Lipo presented Ø of 101.9 ± 1.3 nm (PDI = 0.245), ζ of +33.8 ± 1.3 mV and %EE = 80 ± 0.84 %. CrataBL-Lipo presented anti-staphylococcal activity (MIC = 0.56 mg/mL to 0.72 mg/mL). CrataBL-Lipo inhibited 45.4 %-75.6 % of biofilm formation. No cytotoxicity of CrataBL-Lipo was found (IC50 > 100 mg/L). CrataBL-Lipo presented EC50 of 1.1 mg/L, presenting autophagy, apoptosis and necrosis as death profile. In addition, CrataBL-Lipo reduced the production of IL-10 and TNF-α levels, causing an immunomodulatory effect. CrataBL-Lipo has a therapeutic potential for the treatment of staphylococcal infections and Chagas disease exhibiting a high degree of selectivity for the microorganism, and immunomodulatory properties.

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Chagas disease is a tropical neglected disease that affects millions of people worldwide, still demanding a more effective and safer therapy, especially in its chronic phase which lacks a treatment that promotes substantial parasitological cure. The technical note of Romanha and collaborators published in 2010 aimed establish a guideline with the set of minimum criteria and decision gates for the development of new agents against Trypanosoma cruzi with the focus on developing new antichagasic drugs. In this sense, the present review aims to update this technical note, bringing the state of the art and new advances on this topic in recent years.

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Escherichia coli has been associated with the induction of colorectal cancer (CRC). Thus, combined therapy incorporating usnic acid (UA) and antibiotics such as ceftazidime (CAZ), co-encapsulated in liposomes, could be an alternative. Coating the liposomes with chitosan (Chi) could facilitate the oral administration of this nanocarrier. Liposomes were prepared using the lipid film hydration method, followed by sonication and chitosan coating via the drip technique. Characterization included particle size, polydispersity index, zeta potential, pH, encapsulation efficiency, and physicochemical analyses. The minimum inhibitory concentration and minimum bactericidal concentration were determined against E. coli ATCC 25922, NCTC 13846, and H10407 using the microdilution method. Antibiofilm assays were conducted using the crystal violet method. The liposomes exhibited sizes ranging from 116.5 ± 5.3 to 240.3 ± 3.5 nm and zeta potentials between +16.4 ± 0.6 and +28 ± 0.8 mV. The encapsulation efficiencies were 51.5 ± 0.2% for CAZ and 99.94 ± 0.1% for UA. Lipo-CAZ-Chi and Lipo-UA-Chi exhibited antibacterial activity, inhibited biofilm formation, and preformed biofilms of E. coli. The Lipo-CAZ-UA-Chi and Lipo-CAZ-Chi + Lipo-UA-Chi formulations showed enhanced activities, potentially due to co-encapsulation or combination effects. These findings suggest potential for in vivo oral administration in future antibacterial and antibiofilm therapies against CRC-inducing bacteria.

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Chagas disease is a tropical neglected disease that affects millions of people worldwide, still demanding a more effective and safer therapy, especially in its chronic phase which lacks a treatment that promotes substantial parasitological cure. The technical note of Romanha and collaborators published in 2010 aimed establish a guideline with the set of minimum criteria and decision gates for the development of new agents against Trypanosoma cruzi with the focus on developing new antichagasic drugs. In this sense, the present review aims to update this technical note, bringing the state of the art and new advances on this topic in recent years.

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Asymptomatic Leishmania infantum, when associated with HIV, can become severe and potentially fatal. In this co-infection, the worst prognosis may be influenced by the host's immunological aspects, which are crucial in determining susceptibility. Chemokines play an important role in this process by influencing the cellular composition at affected sites and impacting the disease's outcome. Therefore, the aim of this study was to evaluate proinflammatory chemokines in HIV patients with the asymptomatic L. infantum infection. In this cross-sectional study, the levels of CCL2, CCL5, CXCL8, MIG, and IP-10 were measured in 160 serum samples from co-infected patients (n = 53), patients with HIV (n = 90), and negative controls (n = 17). Quantification was determined by flow cytometry. The obtained data were statistically analyzed using the Kruskal-Wallis test, followed by the Dunn's post-test and the Spearman's correlation coefficient. Significance was set at p < 0.05. The chemokines CCL2, CCL5, MIG, and IP-10 exhibited higher levels in the HIV group compared to co-infection. However, the elevated levels of all these chemokines and their increased connectivity in co-infected patients appear to be important in identifying proinflammatory immune responses associated with the asymptomatic condition. Furthermore, a weak negative correlation was observed between higher levels of CXCL8 and lower viral loads in co-infected patients.

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In this context, the objective of this work was to isolate an alkaline lignin from the leaves of C. ferrea, in addition to investigating different biological activities and its use in the production of releasing tablets in vitro. Initially, the analysis of the composition of the leaves was performed, the contents were: cellulose (33.09 ± 0.3 %), hemicellulose (25.13 ± 0.1 %), lignin (18.29 ± 0.1 %), extractives (17.28 ± 1.0 %) and ash (6.20 ± 0.1 %). The leaves were fractionated to obtain alkaline lignin. The yield of obtaining lignin was 80.12 ± 0.1 %. The obtained lignin was characterized by the techniques: elemental analysis, FTIR, UV/Vis, 2D-NMR, GPC, TGA/DTG, DSC and PY-GC/MS. The results showed that the lignin obtained is of the GSH type, of low molecular weight and thermally stable. The in vitro antioxidant activity was evaluated by different assays promoting results only for DPPH (559.9 ± 0.8 µg/mL) and ABTS (484.1 ± 0.1 µg/mL) being able to promote low antioxidant activity. In addition, it showed low cytotoxicity in normal mammalian cells and promising antitumor and trypanocidal activity. Regarding antimicrobial activity, it was able to inhibit the growth of a strain of Staphylococcus aureus resistant to methicillin, presenting MIC values equal to the standard antibiotic oxacillin. It was also able to inhibit a strain of Candida albicans HAM13 sensitive to fluconazole. In addition, lignin promoted a synergistic effect by promoting a decrease in MIC against these two strains evaluated. Finally, lignin proved to be an excipient with potential for controlled release of antimicrobials.

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Chagas' disease affects approximately eight million people throughout the world, especially the poorest individuals. The protozoan that causes this disease-Trypanosoma cruzi-has the enzyme cruzipain, which is the main therapeutic target. As no available medications have satisfactory effectiveness and safety, it is of fundamental importance to design and synthesize novel analogues that are more active and selective. In the present study, molecular docking and the in silico prediction of ADMET properties were used as strategies to optimize the trypanocidal activity of the pyrimidine compound ZN3F based on interactions with the target site in cruzipain. From the computational results, eight 4-amino-5-carbonitrile-pyrimidine analogues were proposed, synthesized (5a-f and 7g-h) and, tested in vitro on the trypomastigote form of the Tulahuen strain of T. cruzi. The in silico study showed that the designed analogues bond favorably to important amino acid residues of the active site in cruzipain. An in vitro evaluation of cytotoxicity was performed on L929 mammal cell lines. All derivatives inhibited the Tulahuen strain of T. cruzi and also exhibited lower toxicity to L929 cells. The 5e product, in particular, proved to be a potent, selective (IC50 = 2.79 ± 0.00 µM, selectivity index = 31.3) inhibitor of T. cruzi. The present results indicated the effectiveness of drugs based on the structure of the receptor, revealing the potential trypanocidal of pyrimidines. This study also provides information on molecular aspects for the inhibition of cruzipain.

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Malaria can be caused by several Plasmodium species and the development of an effective vaccine is challenging. Currently, the most effective tool to control the disease is the administration of specific chemotherapy; however, resistance to the frontline antimalarials is one of the major problems in malaria control and thus the development of new drugs becomes urgent. The study presented here sought to evaluate the antimalarial activities of compounds derived from 2-amino-1,4-naphthoquinones containing 1,2,3-triazole using in vivo and in vitro models. 1H-1,2,3-Triazole 2-amino-1,4-naphthoquinone derivatives were synthesized and evaluated for antimalarial activity in vitro, using P. falciparum W2 chloroquine (CQ) resistant strain and in vivo using the murine-P. berghei ANKA strain. Acute toxicity was determined as established by the OECD (2001). Cytotoxicity was evaluated against HepG2 and Vero mammalian cell lines. Transmission electron microscopy of the Plasmodium falciparum trophozoite (early and late stages) was used to evaluate the action of compounds derived at ultra-structural level. The compounds displayed low cytotoxicity CC50 > 100 µM, neither did they cause hemolysis at the tested doses and nor the signs of toxicity in the in vivo acute toxicity test. Among the five compounds tested, one showed IC50 values in submicromolar range of 0.8 µM. Compounds 7, 8 and 11 showed IC50 values < 5 µM, and selectivity index (SI) ranging from 6.8 to 343 for HepG2, and from 13.7 to 494.8 for Vero cells. Compounds 8 and 11 were partially active against P. berghei induced parasitemia in vivo. Analysis of the ultrastructural changes associated with the treatment of these two compounds, showed trophozoites with completely degraded cytoplasm, loss of membrane integrity, organelles in the decomposition stage and possible food vacuole deterioration. Our results indicated that compounds 8 and 11 may be considered hit molecules for antimalarial drug discovery platform and deserve further optimization studies.

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The present work reports the synthesis of a novel series of pyridine-thiazolidinones with anti-Trypanosoma cruzi and leishmanicidal activities (compounds 10-27), derived from 2 or 4-pyridine thiosemicarbazones (1-9). The in vitro assays were performed with Trypanosoma cruzi trypomastigotes and amastigotes, as well as with Leishmania amazonensis promastigotes and amastigotes. The cytotoxicity profile was evaluated using the cell line RAW 264.7. From the 18 pyridine-thiazolidinones, 5 were able to inhibit trypomastigotes. Overall, all compounds inhibited amastigotes, highlighting compounds 15 (0.60 µM), 18 (0.64 µM), 17 (0.81 µM), and 27 (0.89 µM). Compounds 15 and 18 were able to induce parasite cell death through necrosis induction. Analysis by scanning electron microscopy showed that T. cruzi trypomastigotes treated with compounds 15 and 18 induced morphological changes such as shortening, retraction and curvature of the parasite body and leakage of internal content. Regarding the antiparasitic evaluation against Leishmania amazonensis, only compound 27 had a higher selectivity compared to Miltefosine against the amastigote form (IC50 = 5.70 µM). Our results showed that compound 27 presented an antiparasitic activity for both Trypanosoma cruzi and Leishmania amazonensis. After in silico evaluation, it was suggested that the new pyridine-thiazolidinones had an appropriate drug-likeness profile. Our results pointed out a new chemical frame with an anti-Trypanosomatidae profile. The pyridine-thiazolidinones presented here for the first time could be used as a starting point for the development of new antiparasitic agents.

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Cutaneous Leishmaniasis (CL) is a Neglected Tropical Disease characterized by skin ulcers caused by Leishmania spp. protozoans and there is no safe and effective vaccine to reduce its negative consequences. In a previous work by our group, we identified T cell epitopes of Leishmania (Viannia) braziliensis which stimulated patients' T cells in vitro. In the present work, the peptides were tested as two pools for their ability to rescue memory T cells during natural infection by Leishmania. We analyzed the frequency of central memory (TCM, CD45RA-CD62L+) and effector memory (TEM, CD45RA + CD62L-) cells during active CL and post-treatment. In parallel, we investigated cell proliferation levels and the cytokines produced after stimulation. Interestingly, we observed higher frequencies (%) in CD4+ TEM during CL, and CD8+ TEM and CD8+ TCM during CL and post-treatment. Cell proliferation was increased, and a significant difference in expression was observed on T-bet and RORγT. Besides that, IFN-γ, IL-2, and IL-10 were detected in patient samples. Collectively, this dataset suggests that during CL there is an increase in the frequency of TCM and TEM, especially in the CD8 compartment. These results indicate a potentially immunogenic profile of the peptide pools, which can support the development of anti-Leishmania formulations.

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The aim of this work was to define the population of regulatory T cells (Tregs) which are circulating in the blood of Leishmania infected individuals clinically displaying a lesion (active disease-AD) and sub-clinical (SC) ones. We have individually collected blood samples, processed the PBMC and stained with fluorochrome-conjugated antibodies against CD3, CD4, Foxp3, CD25, CTLA-4, Ki-67, CCR4, CCR5, and CCR7. Cells were analyzed by flow cytometry. Our results suggest that CD25 and CTLA-4 are upregulated in Tregs of AD patients when compared to SC and uninfected (UN) controls. Moreover, Tregs proliferate upon infection based on Ki-67 nuclear antigen staining. Finally, we have observed that these Tregs of SC and AD patients upregulate CCR4, but not CCR5 and CCR7. There is an increase in the number of circulating Tregs in the blood of Leishmania infected individuals. These cells are potentially more suppressive based on the increased upregulation of CD25 and CTLA-4 during clinical infection (AD) when compared to SC infection. Tregs of both SC and AD cohorts are proliferating and express CCR4, which potentially guide them to the skin, but do not upregulate CCR5 and CCR7.

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COVID-19 is an infectious respiratory disease caused by SARS-CoV-2. Pentraxin 3 (PTX3) is involved in the activation and regulation of the complement system, demonstrating an important role in the pathogenesis of COVID-19. The aim was to evaluate the association of single nucleotide polymorphisms in PTX3 and its plasma levels with the severity of COVID-19. This is a retrospective cohort study, carried out between August 2020 and July 2021, including patients with confirmed COVID-19 hospitalized in 2 hospitals in the Northeast Region of Brazil. Polymorphisms in PTX3 (rs1840680 and rs2305619) were determined by real-time PCR. PTX3 plasma levels were measured by ELISA. Serum levels of interleukin (IL)-6, IL-8, and IL-10 were determined by flow cytometry. A multivariate logistic regression model was used to identify parameters independently associated with COVID-19 severity. P values < 0.05 were considered significant. The study included 496 patients, classified as moderate (n = 267) and severe (n = 229) cases. The PTX3 AA genotype (rs1840680) was independently associated with protection against severe COVID-19 (P = 0.037; odds ratio = 0.555). PTX3 plasma levels were significantly associated with COVID-19 severity and mortality (P < 0.05). PTX3 levels were significantly correlated with IL-6, IL-8, IL-10, C-reactive protein, total leukocytes, neutrophil-to-lymphocyte ratio, urea, creatinine, ferritin, length of hospital stay, and higher respiratory rate (P < 0.05). Our results revealed a protective effect of the PTX3 AA genotype (rs1840680) on the development of severe forms of COVID-19. Additionally, PTX3 plasma levels were associated with the severity of COVID-19. The results of this study provide evidence of an important role of PTX3 in the immunopathology of COVID-19.

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BACKGROUND: Visceral leishmaniasis (VL) remains an important infectious disease worldwide. VL-HIV coinfected individuals can present with atypical clinical forms of VL and have a high risk of VL relapse. Some cytokines have been described as potential markers to diagnose active VL and to predict the severity of the cases. However, few studies have included VL-HIV coinfected patients. We aimed to characterize the levels of several cytokines among VL-HIV coinfected individuals living in a VL-endemic area in Northeast Brazil. METHODS: This was a retrospective, cross-sectional study, aiming to estimate the levels of various cytokines in symptomatic and asymptomatic VL-HIV coinfected individuals. There were 134 study participants (35 symptomatic VL-HIV, 75 asymptomatic VL-HIV, and 24 healthy controls), all ≥ 18 years-old. Serum cytokine levels (interferon-γ, tumor necrosis factor, and interleukins 2, 4, 6, 10, and 17A) were quantified using the Becton Dickinson-BD's Cytometric Bead Array (CBA) system. RESULTS: The population mainly consisted of men (64.9%), with a median age of 35 (27-41) years. Asymptomatic individuals were younger (p = 0.013), with more years of education (p < 0.001), and were more often on antiretroviral therapy (p < 0.001) than those in the symptomatic group. Hemoglobin levels (p < 0.001), lymphocytes (p < 0.001) and CD4 count (p < 0.001) were lower in symptomatic individuals, while HIV viral loads were higher (p < 0.001). In the symptomatic VL-HIV coinfected group, we observed increased serum levels of IL-17A, IL-6, and IL-10 compared to asymptomatic patients and the healthy controls. There were no differences in the levels of all cytokines between asymptomatic VL-HIV coinfected individuals and the healthy controls. CONCLUSIONS: Higher serum levels of IL-17A, IL-6, and IL-10 cytokines were observed in symptomatic coinfected individuals but not in asymptomatically infected individuals. More studies among HIV-positive persons are needed to better understand the role of serum cytokines for prognosis, to define cure and predict VL relapses in VL-HIV coinfected individuals.

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[This corrects the article DOI: 10.3389/fcimb.2022.826039.].

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Visceral leishmaniasis caused by Leishmania (Leishmania) infantum in Latin America progress with hepatosplenomegaly, pancytopenia, hypergammaglobulinemia, and weight loss and maybe lethal mainly in untreated cases. miRNAs are important regulators of immune and inflammatory gene expression, but their mechanisms of action and their relationship to pathogenesis in leishmaniasis are not well understood. In the present study, we sought to quantify changes in miRNAs associated with immune and inflammatory pathways using the L. (L.) infantum promastigote infected- human monocytic THP-1 cell model and plasma from patients with visceral leishmaniasis. We identified differentially expressed miRNAs in infected THP-1 cells compared with non-infected cells using qPCR arrays. These miRNAs were submitted to in silico analysis, revealing targets within functional pathways associated with TGF-ß, chemokines, glucose metabolism, inflammation, apoptosis, and cell signaling. In parallel, we identified differentially expressed miRNAs in active visceral leishmaniasis patient plasma compared with endemic healthy controls. In silico analysis of these data indicated different predicted targets within the TGF-ß, TLR4, IGF-I, chemokine, and HIF1α pathways. Only a small number of miRNAs were commonly identified in these two datasets, notably with miR-548d-3p being up-regulated in both conditions. To evaluate the potential biological role of miR-548d-3p, we transiently transfected a miR-548d-3p inhibitor into L. (L.) infantum infected-THP-1 cells, finding that inhibition of miR-548d-3p enhanced parasite growth, likely mediated through reduced levels of MCP-1/CCL2 and nitric oxide production. Further work will be required to determine how miR-548d-3p plays a role in vivo and whether it serves as a potential biomarker of progressive leishmaniasis.

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American Tegumentary Leishmaniasis (ATL) is an endemic disease in Latin America, mainly caused in Brazil by Leishmania (Viannia) braziliensis. Clinical manifestations vary from mild, localized cutaneous leishmaniasis (CL) to aggressive mucosal disease. The host immune response strongly determines the outcome of infection and pattern of disease. However, the pathogenesis of ATL is not well understood, and host microRNAs (miRNAs) may have a role in this context. In the present study, miRNAs were quantified using qPCR arrays in human monocytic THP-1 cells infected in vitro with L. (V.) braziliensis promastigotes and in plasma from patients with ATL, focusing on inflammatory response-specific miRNAs. Patients with active or self-healed cutaneous leishmaniasis patients, with confirmed parasitological or immunological diagnosis, were compared with healthy controls. Computational target prediction of significantly-altered miRNAs from in vitro L. (V.) braziliensis-infected THP-1 cells revealed predicted targets involved in diverse pathways, including chemokine signaling, inflammatory, cellular proliferation, and tissue repair processes. In plasma, we observed distinct miRNA expression in patients with self-healed and active lesions compared with healthy controls. Some miRNAs dysregulated during THP-1 in vitro infection were also found in plasma from self-healed patients, including miR-548d-3p, which was upregulated in infected THP-1 cells and in plasma from self-healed patients. As miR-548d-3p was predicted to target the chemokine pathway and inflammation is a central to the pathogenesis of ATL, we evaluated the effect of transient transfection of a miR-548d-3p inhibitor on L. (V.) braziliensis infected-THP-1 cells. Inhibition of miR-548d-3p reduced parasite growth early after infection and increased production of MCP1/CCL2, RANTES/CCL5, and IP10/CXCL10. In plasma of self-healed patients, MCP1/CCL2, RANTES/CCL5, and IL-8/CXCL8 concentrations were significantly decreased and MIG/CXCL9 and IP-10/CXCL10 increased compared to patients with active disease. These data suggest that by modulating miRNAs, L. (V.) braziliensis may interfere with chemokine production and hence the inflammatory processes underpinning lesion resolution. Our data suggest miR-548d-3p could be further evaluated as a prognostic marker for ATL and/or as a host-directed therapeutic target.

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BACKGROUND: Visceral leishmaniasis (VL) in HIV-positive individuals is a global health problem. HIV-Leishmania coinfection worsens prognosis and mortality risk, and HIV-Leishmania coinfected individuals are more susceptible to VL relapses. Early initiation of antiretroviral therapy can protect against Leishmania infection in individuals living in VL-endemic areas, and regular use of antiretrovirals might prevent VL relapses in these individuals. We conducted a cross-sectional study in Petrolina, Brazil, an VL-endemic area, to estimate the prevalence of asymptomatic Leishmania cases among HIV-positive outpatients. METHODS: We invited any HIV-positive patients, aged ≥ 18-years-old, under antiretroviral therapy, and who were asymptomatic for VL. Patients were tested for Leishmania with enzyme-linked immunosorbent assays (ELISA)-rK39, immunochromatographic test (ICT)-rK39, direct agglutination test (DAT), latex agglutination test (KAtex), and conventional polymerase chain reaction (PCR). HIV-Leishmania coinfection was diagnosed when at least one VL test was positive. RESULTS: A total of 483 patients were included. The sample was predominantly composed of single, < 48-years-old, black/pardo, heterosexual males, with fewer than 8 years of schooling. The prevalence of asymptomatic HIV-Leishmania coinfection was 9.11% (44/483). HIV mono-infected and HIV-Leishmania coinfected groups differed statistically significantly in terms of race (p = 0.045), marital status (p = 0.030), and HIV viral load (p = 0.046). Black/pardo patients, married patients, and those with an HIV viral load up to 100,000 copies/ml presented higher odds for HIV-Leishmania coinfection. CONCLUSIONS: A considerable number of asymptomatic Leishmania cases were observed among HIV-positive individuals in a VL-endemic area. Given the potential impact on transmission and health costs, as well as the impact on these coinfected individuals, studies of asymptomatic Leishmania carriers can be useful for guiding public health policies in VL-endemic areas aiming to control and eliminate the disease.

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Introdução: O uso de drogas é um grande problema de saúde pública, alterando o estado físico-mental e o comportamento. Nas gestantes, este uso, compromete irreversivelmente a integridade do binômio mãe/feto. A hipótese desta pesquisa foi detectar, pelo ASSIST, se existiria uma alta prevalência de drogadição em gestantes de baixo e alto risco, bem como possíveis fatores de proteção para o não consumo de drogas. Objetivos: Identificar a prevalência de drogadição, avaliar os fatores de proteção e risco relacionados ao uso na gestação através do autorrelato pelo ASSIST. Métodos: Estudo transversal com seleção casuística, número amostral de 160 gestantes, aplicando o ASSIST e seleção por conveniência dos hospitais. Análise inferencial da variável dependente (uso de drogas) e das independentes (idade, escolaridade e estado civil) através da regressão logística com nível de significância 5%. Através de regressão logística multivariada, as variáveis estado civil, escolaridade e idade materna tiveram significância estatística. Resultados: A positividade total do uso de drogas foi de 86,9%, com prevalência de 65% para tabaco, 81,9% álcool, 16,9% maconha, 4,4% cocaína/crack e 12% hipnóticos/sedativo. Ser casada era fator de proteção (p-valor=0,0047 e OR=0,12) junto com ter ensino médio/curso técnico (p-valor=0,041 e OR=0,11); já idade materna superior >24 anos aumentou o uso de drogas (p-valor=0,035). Conclusões: É necessário uma política mais eficaz de assistência e um rastreamento adequado de gestantes usuárias de drogas devido a um alto-risco materno-fetal de complicações clínicas.

Introduction: Drug use is a major public health problem, altering the physicalmental state and behavior. In pregnant women, this use irreversibly compromises the integrity of the mother/fetus binomial. The hypothesis of this research was to detect, by ASSIST, if there was a high prevalence of drug addiction in lowand high-risk pregnant women, as well as possible protective factors for the nonconsumption of drugs. Objectives: To identify the prevalence of drug addiction, to assess the protective and risk factors related to use in pregnancy through selfreporting by ASSIST. Methods: Cross-sectional study with casuistic selection, sample number of 160 pregnant women, applying ASSIST and selection for convenience of hospitals. Inferential analysis of the dependent variable (drug use) and the independent variables (age, education, and marital status) through logistic regression with a 5% significance level. Through multivariate logistic regression, the variables marital status, education and maternal age had statistical significance. Results: The total positivity of drug use was 86.9%, with a prevalence of 65% for tobacco, 81.9% alcohol, 16.9% marijuana, 4.4% cocaine/crack, and 12% hypnotics/sedative. Being married was a protective factor (p-value=0.0047 and OR=0.12) along with having a high school/technical course (p-value=0.041 and OR=0.11); maternal age >24 years old increased the use of drugs (p-value=0.035). Conclusions: A more effective assistance policy and adequate screening of pregnant women who use drugs is necessary due to a high maternal-fetal risk of clinical complications.

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Leishmaniasis is a neglected disease that affects millions of people around the world, mainly socially vulnerable populations and is considered a serious public health problem. Caused by several species of the flagellated protozoa of the Leishmania genus, it is transmitted to man through female sand fly bites. The disease can present the cutaneous, mucocutaneous and visceral clinical forms, varying according to the parasite species and depending on host immune response. Depending on its evolution, the disease may pose serious risks to the afflicted individual's health. In general, treatment for Leishmaniasis is with pentavalent antimonials, in use for approximately 70 years. However, the existing treatment for Leishmaniasis presents drawbacks such as high toxicity, several side effects, cases of resistance, highlighting the need for new efficient therapeutic approaches. Given all the problems that involve the current treatment of leishmaniasis, it is of paramount importance to seek and screen new molecules that have leishmanicidal activity, meet the safety criteria, while presenting low toxicity, low cost, easy administration and that cure efficiently. This review presents some considerations on the leishmaniasis situation, its treatment and the current panorama for the development of new therapies.

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