Estudo epidemiológico das leishmanioses em área de turismo ambiental e ecoturismo, Estado de Mato Grosso do Sul, 2006-2007

The aims of this study were to carry out a serological survey of canine leishmaniasis and identify the phlebotomine fauna in the urban area of Bonito, Mato Grosso do Sul. The serological survey was conducted on a sample of 303 dogs, by means of the indirect immunofluorescence test. Phlebotomines were captured using automated light traps. The serological survey found that 30% of the dogs were seropositive, both from the center and from all districts of the town. A total of 2,772 specimens of phlebotomines were caught and the species most found was Lutzomyia longipalpis (90.4%), which corroborated its role as the vector of for canine visceral leishmaniasis in the region. Phlebotomines of the species Bichromomyia flaviscutellata (the main vector for Leishmania (Leishmania) amazonensis) and Nyssomyia whitmani (the vector for Leishmania (Viannia) brasiliensis) were also caught. The findings indicate the need for continuous epidemiological surveillance, with attention towards diminishing the vector breeding sites and the transmission of these diseases in that region.O presente trabalho teve por objetivo proceder ao levantamento sorológico para leishmanioses em cães e identificar a fauna flebotomínea da zona urbana de Bonito, Mato Grosso do Sul. O inquérito sorológico foi realizado em amostras de 303 cães com a utilização da reação de imunofluorescência indireta. As capturas de flebotomíneos realizaram-se com armadilhas automáticas luminosas. O inquérito sorológico identificou 30% cães reagentes procedentes do centro e de todos os bairros da cidade. Foram capturados 2,772 exemplares de flebotomineos, sendo a espécie mais freqüente foi Lutzomyia longipalpis (90.4%), o que corrobora o seu papel de vetora de leishmaniose visceral canina na região. Foram capturados, também, flebotomíneos da espécie Bichromomyia flaviscutellata, principal vetora da Leishmania (Leishmania) amazonensis, e Nyssomyia whitmani, vetora da Leishmania (Viannia) braziliensis. Os achados indicam a necessidade de uma contínua vigilância epidemiológica, atentando para a diminuição dos criadouros dos vetores e da transmissão desses agravos naquela região.Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Manoel de Barros Foundatio

Spatio-temporal modeling of visceral leishmaniasis in Midwest Brazil: An ecological study of 18-years data (2001-2018).

Visceral leishmaniasis (VL) is a neglected vector-borne disease associated with socioeconomic and environmental issues. In Brazil, epidemics of VL have occurred in major cities since 1980. Applied models for medical and epidemiological research have been used to assess the distribution and characteristics of disease endpoints and identify and characterize potential risk factors. This study described the demographic features of VL and modeled the spatio-temporal distribution of human VL cases and their relationship with underlying predicitve factors using generalized additive models. We conducted an ecological study covering an 18-year period from the first report of an autochthonous case of VL in Campo Grande, state of Mato Grosso do Sul, in 2001 to 2018. The urban area of the city has 74 neighborhoods, and they were the units of analysis of our work. Socioeconomic and demographic data available from Brazilian public databases were considered as covariables. A total of 1,855 VL cases were reported during the study period, with an annual mean incidence rate of 13.23 cases per 100,000 population and a cumulative crude incidence of 235.77 per 100,000 population. The results showed the rapid transition from epidemic to endemic and the centrifugal dispersal pattern of the disease. Moreover, the model highlighted that the urban quality of life index, which is calculated based on income, education, housing conditions, and environmental sanitation data, plays a role in VL occurrence. Our findings highlighted the potential for improving spatio-temporal segmentation of control measures and the cost-effectiveness of integrated disease management programs as soon as VL is difficult to control and prevent and has rapid geographical dispersion and increased incidence rates

In vitro activity of the hydroethanolic extract and biflavonoids isolated from Selaginella sellowii on Leishmania (Leishmania) amazonensis

This study is the first phytochemical investigation of Selaginella sellowii and demonstrates the antileishmanial activity of the hydroethanolic extract from this plant (SSHE), as well as of the biflavonoids amentoflavone and robustaflavone, isolated from this species. The effects of these substances were evaluated on intracellular amastigotes of Leishmania (Leishmania) amazonensis, an aetiological agent of American cutaneous leishmaniasis. SSHE was highly active against intracellular amastigotes [the half maximum inhibitory concentration (IC50) = 20.2 µg/mL]. Fractionation of the extract led to the isolation of the two bioflavonoids with the highest activity: amentoflavone, which was about 200 times more active (IC50 = 0.1 μg/mL) and less cytotoxic than SSHE (IC50 = 2.2 and 3 μg/mL, respectively on NIH/3T3 and J774.A1 cells), with a high selectivity index (SI) (22 and 30), robustaflavone, which was also active against L. amazonensis (IC50 = 2.8 µg/mL), but more cytotoxic, with IC50 = 25.5 µg/mL (SI = 9.1) on NIH/3T3 cells and IC50 = 3.1 µg/mL (SI = 1.1) on J774.A1 cells. The production of nitric oxide (NO) was lower in cells treated with amentoflavone (suggesting that NO does not contribute to the leishmanicidal mechanism in this case), while NO release was higher after treatment with robustaflavone. S. sellowii may be a potential source of biflavonoids that could provide promising compounds for the treatment of cutaneous leishmaniasis

In vivo antileishmanial activity and chemical profile of polar extract from Selaginella sellowii

The polar hydroethanolic extract from Selaginella sellowii(SSPHE) has been previously proven active on intracellular amastigotes (in vitro test) and now was tested on hamsters infected with Leishmania (Leishmania) amazonensis (in vivo test). SSPHE suppressed a 100% of the parasite load in the infection site and draining lymph nodes at an intralesional dose of 50 mg/kg/day × 5, which was similar to the results observed in hamsters treated with N-methylglucamine antimonate (Sb) (28 mg/Kg/day × 5). When orally administered, SSPHE (50 mg/kg/day × 20) suppressed 99.2% of the parasite load in infected footpads, while Sb suppressed 98.5%. SSPHE also enhanced the release of nitric oxide through the intralesional route in comparison to Sb. The chemical fingerprint of SSPHE by high-performance liquid chromatography with diode-array detection and tandem mass spectrometry showed the presence of biflavonoids and high molecular weight phenylpropanoid glycosides. These compounds may have a synergistic action in vivo. Histopathological study revealed that the intralesional treatment with SSPHE induced an intense inflammatory infiltrate, composed mainly of mononuclear cells. The present findings reinforce the potential of this natural product as a source of future drug candidates for American cutaneous leishmaniasis

Flavonoid Derivatives as New Potent Inhibitors of Cysteine Proteases: An Important Step toward the Design of New Compounds for the Treatment of Leishmaniasis

Leishmaniasis is a neglected tropical disease, affecting more than 350 million people globally. However, there is currently no vaccine available against human leishmaniasis, and current treatment is hampered by high cost, side-effects, and painful administration routes. It has become a United Nations goal to end leishmaniasis epidemics by 2030, and multitarget drug strategy emerges as a promising alternative. Among the multitarget compounds, flavonoids are a renowned class of natural products, and a structurally diverse library can be prepared through organic synthesis, which can be tested for biological effectiveness. In this study, we synthesised 17 flavonoid analogues using a scalable, easy-to-reproduce, and inexpensive method. All synthesised compounds presented an impressive inhibition capacity against rCPB2.8, rCPB3, and rH84Y enzymes, which are highly expressed in the amastigote stage, the target form of the parasite. Compounds 3c, f12a, and f12b were found to be effective against all isoforms. Furthermore, their intermolecular interactions were also investigated through a molecular modelling study. These compounds were highly potent against the parasite and demonstrated low cytotoxic action against mammalian cells. These results are pioneering, representing an advance in the investigation of the mechanisms behind the antileishmanial action of flavonoid derivatives. Moreover, compounds have been shown to be promising leads for the design of other cysteine protease inhibitors for the treatment of leishmaniasis diseases

In Vitro antileishmania activity of sesquiterpene-rich essential oils from Nectandra species

Context: New antileishmanias are needed because of toxicity, high cost and resistance problems associated with available drugs. Nectandra (Lauraceae) produces several classes of compounds but its essential oil has not previously been reported to have antileishmania activity. Objective: We evaluated the cytotoxicity and antileishmania activity of essential oils from Nectandra amazonum Nees, N. gardneri Meisn., N. hihua (Ruiz & Pav.) Rohwer and N. megapotamica (Spreng.) Mez. Materials and methods: Nectandra oils were extracted from stem bark/leaves by hydrodistillation and compounds were identified by GC-MS. Oils were tested against Leishmania infantum and L. amazonensis intracellular amastigotes and nitric oxide production was evaluated. Cytotoxicity was achieved on NIH/3T3 and J774.A1 cells for the selectivity index (SI). Results and discussion: Nectandra gardneri was active against L. infantum and L. amazonensis (IC50 =  2.7 ± 1.3/2.1 ± 1.06 μg/mL) and contained 85.4% sesquiterpenes, of which 58.2% was intermediol. Besides low cytotoxicity (SI >11.3), N. gardneri induced a significant increase in NO production by L. infantum-infected macrophages. Nectandra hihua had the best activity on L. infantum amastigotes (IC50 =  0.2 ± 1.1 μg/mL). This oil was 89.0% sesquiterpenes, with 28.1% bicyclogermacrene. The two specimens of N. megapotamica had different activities on amastigotes. The one richer in sesquiterpenes (49.9%) was active against both species (IC50 =  12.5 ± 1.4/21.3 ± 1.2) and had phenylpropanoid E-asarone as the main compound (42.4%). Nectandra amazonum showed moderate activity on both the species (IC50 =  31.9 ± 2.0/22.1 ± 1.3 μg/mL) and low selectivity (0.9 2.6), probably due to the major presence of β-caryophyllene (28.5%). Conclusions: Our data identify compounds that can now be isolated and used for the development of new antileishmanias