Immunological mechanisms involved in macrophage activation and polarization in schistosomiasis.

Human schistosomiasis is caused by helminths of the genus Schistosoma. Macrophages play a crucial role in the immune regulation of this disease. These cells acquire different phenotypes depending on the type of stimulus they receive. M1 macrophages can be 'classically activated' and can display a proinflammatory phenotype. M2 or 'alternatively activated' macrophages are considered anti-inflammatory cells. Despite the relevance of macrophages in controlling infections, the role of the functional types of these cells in schistosomiasis is unclear. This review highlights different molecules and/or macrophage activation and polarization pathways during Schistosoma mansoni and Schistosoma japonicum infection. This review is based on original and review articles obtained through searches in major databases, including Scopus, Google Scholar, ACS, PubMed, Wiley, Scielo, Web of Science, LILACS and ScienceDirect. Our findings emphasize the importance of S. mansoni and S. japonicum antigens in macrophage polarization, as they exert immunomodulatory effects in different stages of the disease and are therefore important as therapeutic targets for schistosomiasis and in vaccine development. A combination of different antigens can provide greater protection, as it possibly stimulates an adequate immune response for an M1 or M2 profile and leads to host resistance; however, this warrants in vitro and in vivo studies.

Praziquantel: An update on the mechanism of its action against schistosomiasis and new therapeutic perspectives.

Praziquantel (PZQ) is the drug of choice for the treatment of all forms of schistosomiasis, although its mechanisms of action are not completely understood. PZQ acts largely on adult worms. This narrative literature review describes what is known about the mechanisms of action of PZQ against schistosomes from in vitro and in vivo studies and highlights the molecular targets in parasites and immune responses induced in definitive hosts by this drug. Moreover, new therapeutic uses of PZQ are discussed. Studies have demonstrated that in addition to impacting voltage-operated Ca2 + channels, PZQ may interact with other schistosome molecules, such as myosin regulatory light chain, glutathione S-transferase, and transient receptor potential channels. Following PZQ administration, increased T regulatory type 1 (Tr1) cell differentiation and decreased inflammation were observed, indicating that PZQ promotes immunoregulatory pathways. Although PZQ is widely used in mass drug administration schemes, the existence of resistant parasites has not been proven; however, it is a concern that should be constantly investigated in human populations. In addition, we discuss studies that evaluate health applications of PZQ (other than helminth infection), such as its effect in cancer therapy and its adjuvant action in vaccines against viruses.

Alterations in blood glucose concentration in wild rodents, Holochilus sciureus, naturally infected with Schistosoma mansoni.

The present study aimed to evaluate the changes in peripheral blood glucose concentrations induced by Schistosoma mansoni infection in Holochilus sciureus rodents, a wild reservoir of the parasite. Glucose concentration was measured in the plasma of blood samples using a colorimetric enzymatic test. Biological parameters and S. mansoni burden in each rodent were also verified and correlated with glucose concentrations. A total of 76 H. sciureus were captured, out of which 20 (26%) were infected with S. mansoni (n=13 males and n=7 females). Although the parasite burden was comparable between the sexes, blood glucose concentration was lower in infected males and almost unchanged in females. Furthermore, histopathological data revealed that male rodents had a greater hepatic granulomatous inflammatory reaction than females. In addition, we also confirmed that the weight and total length of the analyzed animals had no effect on glucose levels. Therefore, natural infection with S. mansoni in H. sciureus may have a lower impact on glycemic homeostasis in females, which will help us understand the role of these rodents as reservoirs of S. mansoni.

Intense transmission of visceral leishmaniasis in a region of northeastern Brazil: a situation analysis after the discontinuance of a zoonosis control program.

In São Luís, Maranhão, northeastern Brazil, the notification of visceral leishmaniasis (VL) cases intensified in 1982, showing endemic and epidemic patterns. In this city, the Center for Zoonoses Control (CZC) was an organization in charge of the control and prevention of the disease. However, technical and political reasons have led to a significant decline in the periodicity of its activities. Therefore, in this study we evaluated the epidemiological scenario of human visceral leishmaniasis (HVL) and the prevalence of the disease in dogs after the cessation of the CZC activities, covering the period of 2007 to 2016. The seroprevalence of canine leishmaniasis was determined based on clinical and serological profiles. HVL cases were notified using data provided by the Municipal Health Department of São Luís. A seropositivity rate of 45.8% (p = 0.0001) was found among dogs, 54% (p = 0.374) of which were asymptomatic. As for human cases, there were 415 notifications, with an increase in the incidence of the zoonosis observed during the aforementioned period. Thus, it can be inferred that after the control and surveillance activities were curtailed, there was an increase in the number of seropositive animals in circulation, acting as reservoirs of infection for dogs and humans.

Hydroalcoholic extract of Caryocar brasiliense Cambess. leaves affect the development of Aedes aegypti mosquitoes.

INTRODUCTION: Curtailing the development of the aquatic immature stages of Aedes aegypti is one of the main measures to limit their spread and the diseases transmitted by them. The use of plant extracts is a promising approach in the development of natural insecticides. Thus, this research aimed to characterize the inhibitory effect of the hydroalcoholic extract of Caryocar brasiliense leaves on the emergence of adult A. aegypti and the main substances that constitute this extract. METHODS: C. brasiliense leaf extract was prepared by ethanol (70%) extraction. Bioassays using L3 larvae were performed at concentrations of 200, 300, 400, and 500 ppm. We identified the major secondary metabolites present in this extract, and performed toxicity tests on an off-target organism, Danio rerio. RESULTS: We observed a significant delay in the development of A. aegypti larvae mainly at a concentration of 500 ppm, and estimated an emergence inhibition for 50% of the population of 150 ppm. Moreover, the C. brasiliense leaf extracts exhibited low toxicity in D. rerio. The main compounds found in the extract were quercetin, violaxanthin, myricetin3-O-hexoside, methyl-elagic-3-arabinose acid, and isoquercitrin. CONCLUSIONS: Herein, we demonstrate the inhibition of mosquito development by the hydroalcoholic extract of C. brasiliense and suggest substances that may act as active principles.

Effectiveness of a handmade shell-based substrate for the breeding of Biomphalaria glabrata under laboratory conditions.

Efficient snail production is essential for the proper maintenance of the Schistosoma mansoni life cycle in the laboratory. In order to improve the breeding of Biomphalaria glabrata under laboratory conditions, this study aimed to demonstrate the effectiveness of a handmade shell-based substrate on the physiological performance of B. glabrata. The shells used to make the substrate were cleaned, sterilized and macerated until a powder was obtained (yield of 92.3%). B. glabrata specimens were randomly assigned to three treatment groups: negative control group (NCG) exposed to a clay-only substrate; a positive control group (PCG) containing clay, oyster flour and calcium carbonate; and the test group (TG) with the shell-based substrate and clay. B. glabrata bred in the test group showed improved growth, sexual maturity, fertility, mortality rate, and shell morphology when compared to the NCG, and similar to the PCG. Therefore, the shell-based substrate proved to be efficient and has a low cost for the breeding of B. glabrata.

Hydroalcoholic extract of Caryocar brasiliense Cambess. leaves affect the development of Aedes aegypti mosquitoes

Abstract INTRODUCTION: Curtailing the development of the aquatic immature stages of Aedes aegypti is one of the main measures to limit their spread and the diseases transmitted by them. The use of plant extracts is a promising approach in the development of natural insecticides. Thus, this research aimed to characterize the inhibitory effect of the hydroalcoholic extract of Caryocar brasiliense leaves on the emergence of adult A. aegypti and the main substances that constitute this extract. METHODS: C. brasiliense leaf extract was prepared by ethanol (70%) extraction. Bioassays using L3 larvae were performed at concentrations of 200, 300, 400, and 500 ppm. We identified the major secondary metabolites present in this extract, and performed toxicity tests on an off-target organism, Danio rerio. RESULTS: We observed a significant delay in the development of A. aegypti larvae mainly at a concentration of 500 ppm, and estimated an emergence inhibition for 50% of the population of 150 ppm. Moreover, the C. brasiliense leaf extracts exhibited low toxicity in D. rerio. The main compounds found in the extract were quercetin, violaxanthin, myricetin3-O-hexoside, methyl-elagic-3-arabinose acid, and isoquercitrin. CONCLUSIONS: Herein, we demonstrate the inhibition of mosquito development by the hydroalcoholic extract of C. brasiliense and suggest substances that may act as active principles.

Parasitological and histological aspects of Holochilus sciureus naturally infected by Schistosoma mansoni / Aspectos parasitológicos e histológicos de Holochilus sciureus naturalmente infectados por Schistosoma mansoni

Abstract Schistosomiasis is a neglected disease that affects millions of people around the world, being common in the state of Maranhão. A total of 225 rodents of the Holochilus sciureus species from the Western Lowland Maranhão were studied, of which 144 animals (64%) exhibited Schistosoma eggs in their feces samples. Macroscopic lesions characterized as well-defined whitish areas on the liver and spleen surfaces were observed. Histopathological examination revealed multifocal granulomas in the esophagus, liver, spleen, pancreas and duodenum, with structures compatible with Schistosoma mansoni eggs, as well as severe hepatic micro-vacuolar degeneration, multifocal and coalescent, with proliferation of random bile ducts and associated epithelial hyperplasia to areas of fibrosis. Adult forms of the parasite were observed in the blood vessels of the portal space. The lungs exhibited moderate and diffuse interstitial pneumonia with intralesional S. mansoni eggs. In the kidneys, hyaline cylinders were observed in the pelvis and diffuse hemorrhage. In conclusion, H. sciureus displays a pathological picture similar to human being. This rodent plays a role as sentinel in Baixada Maranhense.

Resumo A esquistossomose é uma doença negligenciada que afeta milhões de pessoas em todo o mundo, sendo comum no estado do Maranhão. Um total de 225 roedores da espécie Holochilus sciureus da Planície Ocidental do Maranhão foram estudados, dos quais 144 animais (64%) apresentaram ovos de Schistosoma em suas fezes. Lesões macroscópicas caracterizadas como áreas esbranquiçadas bem definidas nas superfícies do fígado e baço foram observadas. O exame histopatológico revelou granulomas multifocais no esôfago, fígado, baço, pâncreas e duodeno, com estruturas compatíveis com ovos de Schistosoma mansoni, degeneração micro-vacuolar hepática grave, multifocal e coalescente, com proliferação de ductos biliares aleatórios e hiperplasia epitelial associada a áreas de fibrose. Formas adultas do parasito foram observadas nos vasos sanguíneos do espaço portal. Os pulmões exibiram pneumonia intersticial moderada e difusa com ovos de S. mansoni intralesionais. Nos rins, foram observados cilindros hialinos na pelve e hemorragia difusa. Em conclusão, H. sciureus apresenta um quadro patológico semelhante ao ser humano. Este roedor desempenha um papel de sentinela na Baixada Maranhense.

Parasitological and histological aspects of Holochilus sciureus naturally infected by Schistosoma mansoni.

Schistosomiasis is a neglected disease that affects millions of people around the world, being common in the state of Maranhão. A total of 225 rodents of the Holochilus sciureus species from the Western Lowland Maranhão were studied, of which 144 animals (64%) exhibited Schistosoma eggs in their feces samples. Macroscopic lesions characterized as well-defined whitish areas on the liver and spleen surfaces were observed. Histopathological examination revealed multifocal granulomas in the esophagus, liver, spleen, pancreas and duodenum, with structures compatible with Schistosoma mansoni eggs, as well as severe hepatic micro-vacuolar degeneration, multifocal and coalescent, with proliferation of random bile ducts and associated epithelial hyperplasia to areas of fibrosis. Adult forms of the parasite were observed in the blood vessels of the portal space. The lungs exhibited moderate and diffuse interstitial pneumonia with intralesional S. mansoni eggs. In the kidneys, hyaline cylinders were observed in the pelvis and diffuse hemorrhage. In conclusion, H. sciureus displays a pathological picture similar to human being. This rodent plays a role as sentinel in Baixada Maranhense.

Spatial and Seasonal Distribution of Holochilus sciureus with Schistosoma mansoni Infection in an Endemic Area for Schistosomiasis in Brazil.

INTRODUCTION: The occurrence of wild rodents in the Schistosoma mansoni life cycle may increase the transmission of schistosomiasis and understanding the spatial and seasonal distribution of the natural infection of these reservoirs is essential for the development of more effective control strategies. MATERIAL AND METHODS: In this study, Holochilus sciureus rodents were captured from the flooded fields of São Bento city (an endemic area for schistosomiasis in Northeast Brazil), during the dry and rainy seasons. All these sites were georeferenced and the prevalence of S. mansoni was verified by the presence of adult worms in the mesenteric branches and livers of each animal. RESULTS: It was demonstrated that almost half of the animals collected were naturally infected with S. mansoni (45.45%) and this infection was not related to the distance from urban areas. Furthermore, the temperature, precipitation, sex, and weight did not interfere with the H. sciureus infection rates. Interestingly, we found, for the first time, the natural infection of H. sciureus in another endemic city of S. mansoni in Northeast Brazil. CONCLUSIONS: Therefore, the H. sciureus rodent shows a high natural infection rate for S. mansoni in the flooded fields of São Bento, regardless of the weather station, capture distance, and biological aspects. Additionally, we have demonstrated that H. sciureus naturally parasitized with S. mansoni may inhabit a much more extensive area that is currently described in the literature.

Distribuição dos moluscos transmissores da esquistossomose no município endêmico de São Bento, Maranhão, Brasil / Distribution of mollusks that transmit schistosomiasis in the endemic municipality of São Bento, Maranhão, Brazil

Neste estudo, objetivou-se mapear os criadouros de Biomphalaria spp., transmissoras da esquistossomose mansoni, presentes no município de São Bento, localizado na região da Baixada Maranhense, área na qual esta doença é endêmica. Foram visitados 16 dos 22 bairros existentes na cidade durante o período de agosto de 2012 a julho de 2013. Os caramujos foram coletados com auxílio de conchas de captura e pinças, armazenados e transportados para o Laboratório de Parasitologia Humana da Universidade Estadual do Maranhão, em São Luís, onde foram acondicionados em aquários de vidro e alimentados com folhas de alface. Os moluscos foram submetidos à análise parasitológica à procura de estágios larvais de Schistosoma mansoni e identificados pela conquiliologia e por meio de dissecções. Em 18 criadouros mapeados foram obtidos 1.195 exemplares de Biomphalaria glabrata e de B. straminea. Nenhum molusco eliminou cercárias de S. mansoni. Considerando os resultados obtidos e os aspectos epidemiológicos relacionados à transmissão da esquistossomose, o mapeamento das espécies vetoras no município permitirá a localização e identificação dos criadouros, o que poderá auxiliar substancialmente os serviços de saúde locais nas atividades de vigilância e controle da esquistossomose, além de nortear futuros estudos epidemiológicos sobre a esquistossomose mansoni na região da Baixada Maranhense