American tegumentary leishmaniasis is an infectious disease caused by a protozoan of the genus Leishmania. Pentavalent antimonials are the first choice drugs for cutaneous leishmaniasis (CL), although doses are controversial. In a clinical trial for CL we investigated the occurrence of pancreatic toxicity with different schedules of treatment with meglumine antimoniate (MA). Seventy-two patients were allocated in two different therapeutic groups: 20 or 5 mg of pentavalent antimony (Sb⁵⁺⁾/kg/day for 20 or 30 days, respectively. Looking for adverse effects, patients were asked about abdominal pain, nausea, vomiting or anorexia in each medical visit. We performed physical examinations and collected blood to evaluate serum amylase and lipase in the pre-treatment period, and every 10 days during treatment and one month post-treatment. Hyperlipasemia occurred in 54.8% and hyperamylasemia in 19.4% patients. Patients treated with MA 20 mg Sb⁵⁺ presented a higher risk of hyperlipasemia (p = 0.023). Besides, higher MA doses were associated with a 2.05 higher risk ratio (p = 0.003) of developing more serious (moderate to severe) hyperlipasemia. The attributable fraction was 51% in this group. Thirty-six patients presented abdominal pain, nausea, vomiting or anorexia but only 47.2% of those had hyperlipasemia and/ or hyperamylasemia. These findings suggest the importance of the search for less toxic therapeutic regimens for the treatment of CL.

Background: Treatment of cutaneous leishmaniasis (CL) remains challenging since the drugs currently used are quite toxic, thus contributing to lethality unrelated to the disease itself but to adverse events (AE). The main objective was to evaluate different treatment regimens with meglumine antimoniate (MA), in a reference center in Rio de Janeiro, Brazil.Methodology: A historical cohort of 592 patients that underwent physical and laboratory examination were enrolled between 2000 and 2017. The outcome measures of effectiveness were epithelialization and complete healing of cutaneous lesions. AE were graded using a standardized scale. Three groups were evaluated: Standard regimen (SR): intramuscular (IM) MA 10–20 mg Sb⁵⁺/kg/day during 20 days (n = 46); Alternative regimen (AR): IM MA 5 mg Sb⁵⁺/kg/day during 30 days (n = 456); Intralesional route (IL): MA infiltration in the lesion(s) through subcutaneous injections (n = 90). Statistical analysis was performed through Fisher exact and Pearson Chi-square tests, Kruskal-Wallis, Kaplan-Meier and log-rank tests.Results: SR, AR and IL showed efficacy of 95.3%, 84.3% and 75.9%, with abandonment rate of 6.5%, 2.4% and 3.4%, respectively. IL patients had more comorbidities (58.9%; p = 0.001), were mostly over 50 years of age (55.6%), and had an evolution time longer than 2 months (65.6%; p = 0.02). Time for epithelialization and complete healing were similar in IL and IM MA groups (p = 0.9 and p = 0.5; respectively). Total AE and moderate to severe AE that frequently led to treatment interruption were more common in SR group, while AR and IL showed less toxicity.Conclusions/Significance: AR and IL showed less toxicity and may be good options especially in CL cases with comorbidities, although SR treatment was more effective. IL treatment was an effective and safe strategy, and it may be used as first therapy option as well as a rescue scheme in patients initially treated with other drugs.

New world cutaneous leishmaniasis (NWCL) is an anthropozoonosis caused by different species of the protozoan Leishmania. Colorimetric in situ hybridization (CISH) was shown to satisfactorily detect amastigote forms of Leishmania spp. in animal tissues, yet it was not tested for the diagnosis of human NWCL. The aim of this study was to compare CISH, histopathology (HP), and immunohistochemistry (IHC) techniques to diagnose NWCL in human cutaneous lesions. The sample comprised fifty formalin-fixed, paraffin-embedded skin biopsy specimens from patients with NWCL caused by L. (V.) braziliensis. These specimens were analyzed by CISH, using a generic probe for Leishmania, IHC, and HP to assess the sensitivity of these methods by using a parasitological culture as a standard reference. Additional specimens from three patients diagnosed with cutaneous mycoses were also included to evaluate cross-reactions between CISH and IHC. The sensitivities of IHC, CISH, and HP for detecting amastigotes was 66%, 54%, and 50%, respectively. IHC, unlike CISH, cross-reacted with different species of fungi. Together, these results demonstrate that CISH may be a complementary assay for the detection of amastigote in the laboratorial diagnosis routine of human NWCL caused by L. (V.) braziliensis.

Sporotrichosis is a subcutaneous mycosis caused by dimorphic fungi of the genus Sporothrix. The authors report a case of fixed cutaneous sporotrichosis with therapeutic failure after 18 months of itraconazole and terbinafine associated with cryosurgery. The patient was cured after the introduction of saturated potassium iodide solution. Sporothrix brasiliensis was the identified species, presenting a susceptibility profile to itraconazole and terbinafine. This fact suggests that therapeutic failure is probably related to the host-fungus interaction rather than drug resistance. It is possible that the immunomodulatory action of the saturated potassium iodide solution may have played an important role in curing this patient.

Cutaneous leishmaniasis is a neglected tropical disease caused, in Brazil, mainly by Leishmania braziliensis, which is a protozoan transmitted during the blood feeding of infected female sandflies. To control leishmaniasis, the participation of CD4⁺ Th1 cells together with macrophages, neutrophils, and other peripheral blood cells, including platelets, is necessary. These anuclear fragments, when activated, produce microvesicles (MVs) that can reach locations outside the blood, carrying molecules responsible for activating pro-inflammatory responses and antigen presentation. Using flow cytometry, this current study evaluated the frequency and concentration of platelet-derived MVs (pMVs) in plasma samples obtained from patients in the acute phase and undergoing treatment, as well as from healthy volunteers. Our results revealed a higher frequency and concentration of pMVs in the plasma of patients with acute CL when compared to all other groups studied. These results highlight the impact of pMVs in modulating the immune response of CL patients, correlating their higher concentrations and frequencies in CL-patient plasmas, with the acute inflammatory status of the disease and their reduction with beneficial results of systemic treatment with antimony. This knowledge is essential to define potential treatment protocols, as well as highlight pMVs as biomarkers for the different clinical stages of CL.