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1.
Transbound Emerg Dis ; 69(6): 3153-3159, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36057790

RESUMO

Schistosomiasis is a tropical neglected disease commonly associated with rural areas; however, urban schistosomiasis has been reported worldwide, and increasing urbanization is one of the most important demographic shifts of the 20th and now 21st centuries. The pattern of urbanization is not uniform so that within the same city the rates and sources of population increase vary. Here, we report on the parasite composition in one neighbourhood in the metropolitan area of Salvador, Bahia, Brazil. Using epidemiological data and population genetics, we find evidence for local transmission and maintenance of Schistosoma mansoni infection within an urban population and little contribution from rural-urban migration. Our findings provide direction for local mitigation strategies and to assist the public living in this neighbourhood to interrupt the local transmission cycle.


Assuntos
Esquistossomose mansoni , Esquistossomose , Animais , Schistosoma mansoni/genética , Brasil/epidemiologia , Esquistossomose/epidemiologia , Esquistossomose/prevenção & controle , Esquistossomose/veterinária , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/prevenção & controle , Esquistossomose mansoni/veterinária , População Urbana
2.
Acta Trop ; 236: 106677, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36063905

RESUMO

Schistosomiasis is a neglected parasitic disease caused by digenean trematodes from the genus Schistosoma that affects millions of people worldwide. Despite efforts to control its transmission, this disease remains active within several endemic regions of Africa, Asia, and the Americas. In addition to the deficits in sanitation and educational structure, another major obstacle hindering the eradication of schistosomiasis is the ability of Schistosoma spp. to naturally infect multiple vertebrate hosts, particularly wild rodents. Due to climate change and other anthropogenic disturbances, contact between humans and wild animals has increased, and this has contributed to more frequent interactions between Schistosoma species that typically infect different hosts. This new transmission dynamic involving Schistosoma spp., humans, wild rodents, and livestock could potentially increase the frequency of Schistosoma hybridization and the establishment of new genotypes and strains. Although it is not currently possible to precisely measure how this biological phenomenon affects the epidemiology and morbidity of schistosomiasis, we speculate that these Schistosoma variants may negatively impact control strategies, treatment regimens, and disease burden in humans. In the present study, we discuss the natural infections of wild rodents with Schistosoma spp., the role of these animals as Schistosoma spp. reservoirs, and how they may select hybrids and strains of Schistosoma mansoni. We also discuss measures required to shed light on the actual role of the wild rodents Nectomys squamipes and Holochilus sciureus in the transmission and morbidity of schistosomiasis in Brazil.


Assuntos
Esquistossomose mansoni , Esquistossomose , Animais , Animais Selvagens/parasitologia , Humanos , Roedores , Schistosoma mansoni/genética , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/prevenção & controle , Esquistossomose mansoni/veterinária
3.
Rev Bras Parasitol Vet ; 31(2): e021921, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35352759

RESUMO

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.


Assuntos
Doenças dos Roedores , Esquistossomose mansoni , Animais , Glicemia , Feminino , Masculino , Roedores/parasitologia , Schistosoma mansoni , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/veterinária , Sigmodontinae
4.
Parasitol Int ; 83: 102317, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33676013

RESUMO

Granulomas are inflammatory tissue responses directed to a set of antigens. Trapped Schistosoma mansoni eggs promote productive granulomas in the tissues, and they are the main damage caused by schistosomiasis. Some S. mansoni antigenic proteins may have a direct involvement in the resolution of the granulomatous response. The ATP diphosphohydrolases isoforms of this parasite are immunogenic, expressed in all phases of the parasite life cycle and secreted by eggs and adult worms. Potato apyrase is a vegetable protein that cross-reactive with parasite ATP diphosphohydrolases isoforms. In this study, the vegetable protein was purified, before being inoculated in C57BL/6 mice that were later infected with cercariae. Sixty days after infection, adult worms were recovered, antibodies and cytokines were measured, and morphological granuloma alterations evaluated. Immunization of the animals induced significant levels of IgG and IgG1 antibodies and IFN-γ, IL-10 and IL-5 cytokines, but not IL-13, suggesting that potato apyrase is an immunoregulatory protein. Supporting this hypothesis, it was found that liver damage associated with schistosomiasis was mitigated, reducing the size of the areas affected by granuloma to 35% and increasing the presence of multinucleated giant cells in this environment. In conclusion, potato apyrase was found to be effective immunomodulatory antigen for murine schistosomiasis.


Assuntos
Apirase/química , Células Gigantes/efeitos dos fármacos , Doenças dos Roedores/parasitologia , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/veterinária , Solanum tuberosum/química , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/parasitologia , Solanum tuberosum/enzimologia
5.
Front Immunol ; 12: 805882, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35095891

RESUMO

Background: We seek to provide a comprehensive overview of transcriptomics responses of immune-related features of the gastropod Biomphalaria glabrata (Bg) following exposure to Schistosoma mansoni (Sm), a trematode causing human schistosomiasis. Responses of schistosome-susceptible (M line, or SUS) and -resistant (BS-90, or RES) Bg strains were characterized following exposure to Sm for 0.5, 2, 8 or 40 days post-exposure (dpe). Methods: RNA-Seq and differential expression analysis were undertaken on 56 snails from 14 groups. We considered 7 response categories: 1) constitutive resistance factors; 2) constitutive susceptibility factors; 3) generalized stress responses; 4) induced resistance factors; 5) resistance factors suppressed in SUS snails; 6) suppressed/manipulated factors in SUS snails; and 7) tolerance responses in SUS snails. We also undertook a gene co-expression network analysis. Results from prior studies identifying schistosome resistance/susceptibility factors were examined relative to our findings. Results: A total of 792 million paired-end reads representing 91.2% of the estimated 31,985 genes in the Bg genome were detected and results for the 7 categories compiled and highlighted. For both RES and SUS snails, a single most supported network of genes with highly correlated expression was found. Conclusions: 1) Several constitutive differences in gene expression between SUS and RES snails were noted, the majority over-represented in RES; 2) There was little indication of a generalized stress response shared by SUS and RES snails at 0.5 or 2 dpe; 3) RES snails mounted a strong, multi-faceted response by 0.5 dpe that carried over to 2 dpe; 4) The most notable SUS responses were at 40 dpe, in snails shedding cercariae, when numerous features were either strongly down-regulated indicative of physiological distress or parasite manipulation, or up-regulated, suggestive of tolerance or survival-promoting effects; 5) Of 55 genes previously identified in genome wide mapping studies, 29 (52.7%) were responsive to Sm, as were many familiar resistance-associated genes (41.0%) identified by other means; 6) Both network analysis and remarkably specific patterns of expression of lectins and G protein-coupled receptors in categories 4, 6 and 7 were indicative of orchestrated responses of different suites of genes in SUS or RES snails following exposure to Sm.


Assuntos
Biomphalaria/genética , Biomphalaria/parasitologia , Interações Hospedeiro-Parasita/genética , Doenças Parasitárias em Animais/parasitologia , Schistosoma mansoni , Esquistossomose mansoni/veterinária , Animais , Biologia Computacional/métodos , Resistência à Doença/genética , Resistência à Doença/imunologia , Suscetibilidade a Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Interações Hospedeiro-Parasita/imunologia , Anotação de Sequência Molecular , RNA-Seq
6.
Am J Trop Med Hyg ; 103(6): 2278-2281, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32996451

RESUMO

Transmission of Schistosoma mansoni was interrupted on St. Kitts, a Caribbean island, in the 1950s. With no reported cases since that time and most Biomphalaria spp. snail populations eliminated based on surveys in the 1970s, S. mansoni has been considered eliminated on St. Kitts. In 2019, S. mansoni eggs were found in an African green monkey (Chlorocebus aethiops sabaeus) that originated from St. Kitts. Nonhuman primate (NHP) infections have been considered incidental to human infections, with infections in NHPs resolving with the elimination of S. mansoni in the human population. An NHP with S. mansoni infection suggests that the NHP may be able to maintain a reservoir sylvatic cycle. Alternatively, S. mansoni transmission was not eliminated or S. mansoni has been reintroduced to St. Kitts. The occurrence of an infected NHP from St. Kitts supports the need for continuous monitoring in areas where S. mansoni is considered eliminated.


Assuntos
Chlorocebus aethiops/parasitologia , Doenças dos Macacos , Esquistossomose mansoni/prevenção & controle , Esquistossomose mansoni/veterinária , Animais , Erradicação de Doenças , Fezes , Humanos , Óvulo , São Cristóvão e Névis , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/diagnóstico
7.
J Ethnopharmacol ; 247: 112270, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31589965

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Primates forage on a variety of plant parts to balance their dietary intake to meet requirements of energy, nutrition and maintenance, however the reason(s) leading them to ingest some plants which have no nutritional value and/or contain bioactive or even toxic secondary metabolites is recently gaining closer attention. The growing literature suggests that primates consume plants for medicinal purposes (self-medication) as well, particularly when infected with parasites and pathogens (bacteria, viruses, microbes). Interestingly, some of the plants they consume are also used by humans for similar purposes or may have potential uses for humans. MATERIALS AND METHODS: As part of a 16-month study of the parasite ecology of a sub-species of Japanese macaques (Macaca fuscata yakui) on the island of Yakushima, we surveyed their feeding habits and collected a subset of plants and plant parts observed being ingested by macaques. The ethnomedicinal value of these plants was surveyed and methanolic extracts of 45 plant parts were tested in vitro against important parasites of humans, including four protozoan parasites Plasmodium falciparum, Trypanosoma brucei rhodesiense, T. cruzi and Leishmania donovani, and the trematode flatworm Schistosoma mansoni. Potential toxicity of the extracts was also assessed on mammalian cells. RESULTS: A wide range of ethnomedicinal uses in Asia for these plants is noted, with 37% associated with the treatment of parasites, pathogens and related symptoms. Additionally, the 45 extracts tested showed broad and significant activity against our test organisms. All extracts were active against T. b. rhodesiense. The majority (over 80%) inhibited the growth of P. falciparum and L. donovani. Half of the extracts also displayed antiprotozoal potential against T. cruzi while only several extracts were active against both larval and adult stages of S. mansoni. Cytotoxicity was generally low, although several extracts lacked specific toxicity to test parasites. CONCLUSIONS: Our results indicated a number of plants and their parts to have antiparasitic activity not previously reported in the ethnopharmacological literature. Enhanced understanding of the primate diets, particularly during periods of intensified parasite infection risk may help to further narrow down plants of interest for lead compound development. The study of animal self-medication is a complementary approach, with precedence, to drug discovery of new lead drug compounds against human parasitic diseases.


Assuntos
Anti-Helmínticos/farmacologia , Antiprotozoários/farmacologia , Macaca fuscata/parasitologia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Infecções Protozoárias em Animais/tratamento farmacológico , Esquistossomose mansoni/tratamento farmacológico , Animais , Anti-Helmínticos/uso terapêutico , Antiprotozoários/uso terapêutico , Etnofarmacologia , Comportamento Alimentar , Feminino , Ilhas , Japão , Leishmania donovani/efeitos dos fármacos , Leishmania donovani/isolamento & purificação , Masculino , Medicina Tradicional/métodos , Testes de Sensibilidade Parasitária , Extratos Vegetais/uso terapêutico , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/isolamento & purificação , Infecções Protozoárias em Animais/parasitologia , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/veterinária , Automedicação/veterinária , Testes de Toxicidade , Trypanosoma brucei rhodesiense/isolamento & purificação , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/isolamento & purificação
8.
Rev. bras. parasitol. vet ; 28(4): 769-772, Oct.-Dec. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1057975

RESUMO

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.


Assuntos
Animais , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/veterinária , Sigmodontinae/parasitologia , Contagem de Ovos de Parasitas , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/patologia , Fezes/parasitologia
9.
Rev Bras Parasitol Vet ; 28(4): 769-772, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618302

RESUMO

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.


Assuntos
Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/veterinária , Sigmodontinae/parasitologia , Animais , Fezes/parasitologia , Contagem de Ovos de Parasitas , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/patologia
10.
Acta Parasitol ; 64(4): 932-937, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31286359

RESUMO

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.


Assuntos
Distribuição Animal , Roedores/parasitologia , Esquistossomose mansoni/veterinária , Estações do Ano , Análise Espacial , Animais , Animais Selvagens/parasitologia , Brasil/epidemiologia , Vetores de Doenças , Doenças Endêmicas , Feminino , Estágios do Ciclo de Vida , Masculino , Prevalência , Schistosoma mansoni , Esquistossomose mansoni/epidemiologia
11.
Infect Dis Poverty ; 8(1): 32, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077256

RESUMO

BACKGROUND: Reports of natural infections of Schistosoma mansoni in a number of species of nonhuman primates (NHPs) in Africa, coupled with the substantial overlap of NHP habitats and human schistosomiasis endemic areas, has led to concerns about the role of NHPs in the transmission of human schistosomiasis. We conducted a systematic review of the literature to describe the current scope of knowledge for Africa, for the NHP species implicated, their geographical distribution, infection rates with S. mansoni, and to discuss the implications for public health and conservation. MAIN TEXT: A systematic search of the literature was performed using PubMed, Web of Science, Google Scholar, the World Health Organization (WHO) library database, World Cat, and ScienceDirect without any language restriction. Studies examining S. mansoni infection of any African NHP species were included. Study types, primate species, their geographical distribution, and parasite diagnostic techniques reported in the studies were qualitatively summarized. Data for species with sample sizes ≥10 were included in the meta-analysis. We assessed the reported infection rate, and used a random-effects model to estimate the summary infection rates and 95% confidence intervals (CIs). We assessed heterogeneity among studies using the I2 statistics. Twenty-nine publications, from 1960 to 2018, were identified and included in the review. The studies examined a total of 2962 primates belonging to 22 species in 11 genera across ten countries (Cameroon, Eritrea, Ethiopia, Gabon, Kenya, Nigeria, Senegal, Tanzania, Uganda, and Zimbabwe), and S. mansoni infections were found in nine species of five genera in all countries. When we excluded studies with sample sizes < 10, data from 24 studies on 11 species of primates in three genera in ten countries remained in the meta-analysis. The overall pooled estimate of infection rate was 10% (95% CI: 6-16%) with high heterogeneity (I2 = 94.77%) across countries and species/genera. Among the three genera, Pan had the highest infection rate of 15% (95% CI: 0-55%), followed by Papio at 11% (95% CI: 6-18%), and Cercopithecus at 5% (95% CI: 0-14%). The association between NHP and human infections was positive, but not significant, due to low study sample matches and high variation. CONCLUSIONS: Our findings suggest that S. mansoni infection rate is high in African NHPs, with substantial heterogeneities across species/genera and countries in Africa. Given the evidence for potential spillover and spillback of S. mansoni between African NHPs and humans, further research is urgently needed to understand ecology and mechanisms of transmission of the parasite between NHP and human hosts, in order to inform control strategies of this important neglected tropical disease.


Assuntos
Reservatórios de Doenças/parasitologia , Doenças Negligenciadas/veterinária , Primatas/parasitologia , Esquistossomose mansoni/veterinária , África , Animais , Geografia , Humanos , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/parasitologia , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/transmissão
12.
Acta Parasitol ; 64(1): 31-43, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30671771

RESUMO

INTRODUCTION: Pomacea lineata acts as the natural biological controller of Biomphalaria glabrata, the intermediate host of Schistosoma mansoni, as they are found in the same environment. However, there are no studies reporting an infection in P. lineata due to S. mansoni. Thus, this work investigated parameters related to the immunity of P. lineata after exposure for 24 and 48 h to S. mansoni under experimental conditions. METHODS: The F1 generation of these snails was used in this study. The total and differential counts of hemocytes, phenoloxidase, nitric oxide, total proteins, expression of TNF-α in hemocytes and histopathology of the head-foot organ were analyzed. RESULTS: Exposure to S. mansoni promoted an increase in the total number of hemocytes, an increase of granulocytes, a reduction of agranulocytes and hyalinocytes, an increase in phenoloxidase levels, total proteins and nitric oxide. There was TNF-α expression in the agranulocytes and granulocytes, increasing in intensity after exposure to the trematode. Head-foot histopathology revealed the presence of sporocytes in the fibromuscular layer surrounded by granulation tissue only within 24 h. At 48 h, there was marked fibrosis in this layer and little granulation tissue. CONCLUSION: Thus, we can conclude that P. lineata seems to trigger a series of immunological strategies in a very effective way that confers some resistance to S. mansoni.


Assuntos
Resistência à Doença , Gastrópodes/imunologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/veterinária , Animais , Hemócitos/imunologia , Imuno-Histoquímica , Modelos Animais , Monofenol Mono-Oxigenase/análise , Óxido Nítrico/análise , Esquistossomose mansoni/patologia , Fator de Necrose Tumoral alfa/análise
13.
J Infect Dis ; 219(10): 1671-1680, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30561696

RESUMO

Baboons vaccinated with radiation-attenuated cercariae develop high levels of protection against schistosome infection, correlating to high antibody titres towards schistosome antigens with unknown molecular identity. Using a microarray consisting of glycans isolated from different life-stages of schistosomes, we studied the anti-glycan immunoglobulin (Ig) G and IgM responses in vaccinated and challenged baboons over a time course of 25 weeks. Anti-glycan IgM responses developed early after vaccination, but did not rise in response to later vaccinations. In contrast, anti-glycan IgG developed more slowly, but was boosted by all five subsequent vaccinations. High IgM and IgG levels against O-glycans and glycosphingolipid glycans of cercariae were observed. At the time of challenge, while most antibody levels decreased in the absence of vaccination, IgG towards a subset of glycans containing multiple-fucosylated motifs remained high until 6 weeks post-challenge during challenge parasite elimination, suggesting a possible role of this IgG in protection.


Assuntos
Anticorpos Anti-Helmínticos/imunologia , Papio anubis/imunologia , Papio anubis/parasitologia , Schistosoma mansoni/efeitos da radiação , Esquistossomose mansoni/veterinária , Animais , Antígenos de Helmintos/imunologia , Cercárias/imunologia , Cercárias/efeitos da radiação , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Análise em Microsséries/métodos , Polissacarídeos/imunologia , Polissacarídeos/metabolismo , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/prevenção & controle , Vacinação
14.
Bioorg Med Chem Lett ; 28(23-24): 3648-3651, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30389288

RESUMO

Urea carboxylic acids, products of aryl hydantoin hydrolysis, were recently identified as a new antischistosomal chemotype. We now describe a baseline structure-activity relationship (SAR) for this compound series. With one exception, analogs of lead urea carboxylic acid 2 were quite polar with Log D7.4 values ranging from -1.9 to 1.8, had high aqueous solubilities in the range of 25-100 µg/mL, and were metabolically stable. None of the compounds had measurable in vitro antischistosomal activity or cytotoxicity, but four of these had moderate worm burden reduction (WBR) values of 42-70% when they were administered as single 100 mg/kg oral doses to S. mansoni-infected mice. These data indicate that with the exception of the gem-dimethyl substructure and the distal nitrogen atom of the urea functional group, the rest of the structure of 2 is required for in vivo antischistosomal activity.


Assuntos
Ácidos Carboxílicos/química , Esquistossomicidas/química , Ureia/química , Animais , Ácidos Carboxílicos/metabolismo , Ácidos Carboxílicos/farmacologia , Ácidos Carboxílicos/uso terapêutico , Meia-Vida , Humanos , Camundongos , Microssomos Hepáticos/metabolismo , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/veterinária , Esquistossomicidas/metabolismo , Esquistossomicidas/farmacologia , Esquistossomicidas/uso terapêutico , Relação Estrutura-Atividade
15.
PLoS Biol ; 16(10): e2005850, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30379806

RESUMO

Forkhead box P3 (Foxp3+) regulatory T (Treg)-cell function is controlled by environmental cues of which cytokine-mediated signaling is a dominant component. In vivo, interleukin-4 (IL-4)-mediated signaling via IL-4 receptor alpha (IL-4Rα) mediates Treg cell transdifferentiation into ex-Foxp3 T helper 2 (Th2) or T helper 17 (Th17) cells. However, IL-4-mediated signaling also reinforces the Foxp3 Treg compartment in vitro. We generated Foxp3-specific IL-4Rα-deficient mice and demonstrated differential efficiency of IL-4Rα deletion in male (approximately 90%) and female (approximately 40%) animals, because of cyclic recombinase (Cre)-mediated X-linked foxp3 inactivation. Irrespective of the degree of IL-4Rα deletion within the Foxp3+ Treg cell population, mice showed exacerbation of immune effector responses with aggravated tissue pathology in tissue-dwelling helminth infections (Schistosoma mansoni or Nippostrongylus brasiliensis). Mechanistically, IL-4Rα deletion in males and females led to a reduced expression of Foxp3 and subsequently an impaired accumulation of Foxp3+ Treg cells to inflamed tissues. In-depth cellular typing by flow cytometry revealed that the impairment of IL-4Rα-mediated signaling during helminth infections decreased the ability of central Treg cells to convert into effector Treg (eTreg) cells and caused a significant down-regulation of markers associated with Treg cell migration (C-X-C motif chemokine receptor 3 [CXCR3]) and accumulation in inflamed tissues (GATA binding protein 3 [GATA3]) as well as survival (B cell lymphoma 2 [Bcl-2]). These findings unprecedentedly, to our knowledge, uncover a role for IL-4Rα signaling in the positive regulation of Foxp3+ Treg cell function in vivo. Complementing our past knowledge on a widely reported role for IL-4Rα signaling in the negative regulation and transdifferentiation of Foxp3+ Treg cells in vivo, our present findings reveal the host requirement for an intact, but not reduced or potentiated, IL-4Rα-mediated signaling on Foxp3+ Treg cells to optimally control inflammation during helminth infections.


Assuntos
Fatores de Transcrição Forkhead/fisiologia , Helmintíase/imunologia , Receptores de Superfície Celular/fisiologia , Animais , Feminino , Fatores de Transcrição Forkhead/metabolismo , Helmintíase Animal/imunologia , Helmintos/patogenicidade , Inflamação/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Nippostrongylus , Schistosoma mansoni , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/veterinária , Transdução de Sinais , Infecções por Strongylida , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/fisiologia , Células Th17 , Células Th2
16.
J Vector Borne Dis ; 55(2): 116-121, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30280709

RESUMO

BACKGROUND & OBJECTIVES: The transmission of schistosomiasis, caused by trematodes of the genus Schistosoma, relies on freshwater snails that act as an intermediate host while human and other mammalian act as the definitive hosts. Many non-human primates (NHPs) such as Chlorocebus aethiops (vervet) and Papio anubis (baboon) are reported to be infected with Schistosoma mansoni in Ethiopia, but the role they play in parasite maintenance and transmission is still not clear. The objective of this study was, therefore, to determine the prevalence of S. mansoni infection in human and NHPs living in close proximities to villages in selected endemic areas of Ethiopia. METHODS: In this cross-sectional study, stool specimens were collected from 911 humans, and fresh faecal droppings from 106 NHPs from Bochesa (Ziway), Bishan Gari (Kime) and Finchaa (Camp 7) endemic localities in Oromia Regional State, and examined for S. mansoni and other helminth infections using Kato-Katz method for human participants and direct microscopic examination for NHPs. RESULTS: The prevalence of helminthiasis among the human study population was 42.4% (386/911), and for soil-transmitted helminth infections (A. lumbricoides, hookworms, and T. trichiura) it was 13.4% (122/911). In humans S. mansoni was the predominant parasite, 23.1% (210/911) followed by A. lumbricoides, 8.7% (79/911); hookworms, 5.8% (53/911); T. trichiura, 4.8% (44/911); Taenia species, 2.2% (20/911); E. vermicularis, 2.1% (19/911); and H. nana, 3.2% (29/911). NHPs were found positive for Trichuris species and Strongyloides species besides S. mansoni. INTERPRETATION & CONCLUSION: NHPs might play a significant role in local transmission and maintenance of S. mansoni infection even in the absence of human hosts. This calls for supplementation of chemotherapy for schistosomiasis along with measures such as snail control to interrupt transmission of the disease from humans to NHPs, and vice-versa.


Assuntos
Doenças dos Macacos/parasitologia , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/veterinária , Adolescente , Adulto , Idoso , Animais , Criança , Pré-Escolar , Chlorocebus aethiops/parasitologia , Estudos Transversais , Etiópia/epidemiologia , Fezes/parasitologia , Feminino , Helmintíase/epidemiologia , Helmintíase/parasitologia , Helmintíase Animal/epidemiologia , Helmintíase Animal/parasitologia , Helmintos/classificação , Helmintos/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Doenças dos Macacos/epidemiologia , Papio/parasitologia , Schistosoma mansoni/genética , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/epidemiologia , Solo/parasitologia , Adulto Jovem
17.
Parasitol Int ; 67(5): 609-611, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29894729

RESUMO

Parasite-induced behavioral changes in their hosts favor to complete the lifecycle of parasites. Schistosome infection is also known to cause physiological changes in infected freshwater snail intermediate hosts. Here, we report, a novel phenomenon in which Schistosoma mansoni, a highly debilitating worm affecting millions of people worldwide, alters the phototropic behavior of Biomphalaria glabrata, the vector snail. S. mansoni-infection enhanced positive phototropism of vector snails and infected snails spent significantly more time in light. Possibly, these behavioral changes help the parasite to be released efficiently from the infected intermediate hosts, and to infect mammalian hosts.


Assuntos
Comportamento Animal , Biomphalaria/fisiologia , Biomphalaria/parasitologia , Interações Hospedeiro-Parasita , Fototropismo , Esquistossomose mansoni/veterinária , Animais , Vetores de Doenças , Luz , Schistosoma mansoni , Água/parasitologia
18.
BMC Res Notes ; 11(1): 146, 2018 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-29463304

RESUMO

OBJECTIVE: To assess Schistosoma mansoni and other intestinal parasitic infections in schoolchildren and vervet monkeys (Chlorocebus aethiops) in Bochessa Village, Ziway, Ethiopia. RESULTS: Fecal specimens from selected schoolchildren and droppings of the vervet monkeys were collected and microscopically examined for intestinal parasites using the Kato-Katz thick smear and formol-ether concentration techniques. The prevalences of S. mansoni, Trichuris trichiura, Ascaris lumbricoides, Enterobius vermicularis, hookworms, Hymenolepis nana and Taenia species among the children were 35.7, 26.9, 24.1, 2.1, 2.1, 1.07 and 2.1%, respectively (by Kato-Katz) and 39.3, 36.1, 35.6, 2.9, 10.0, 4.3, and 2.9%, respectively (by formol-ether concentration). Prevalence of S. mansoni in vervet monkeys ranged from 10 to 20%. B. pfeifferi snails were exposed to S. mansoni miracidia from vervet origin, shed cercariae were then used to infect lab-bred albino mice. Adult worms were harvested from the mice 5 weeks post-exposure to cercariae to establish the schistosome life cycle and confirm the infection in the vervet monkeys. The natural infection of S. mansoni in vervet monkeys suggests that the non-human primate is likely to be implicated in the local transmission of schistosomiasis. Further epidemiological and molecular studies are needed to fully elucidate zoonotic role of non-human primate in the area.


Assuntos
Chlorocebus aethiops/parasitologia , Enteropatias Parasitárias/epidemiologia , Esquistossomose mansoni/epidemiologia , Zoonoses/epidemiologia , Animais , Criança , Etiópia/epidemiologia , Feminino , Humanos , Enteropatias Parasitárias/transmissão , Enteropatias Parasitárias/veterinária , Masculino , Esquistossomose mansoni/transmissão , Esquistossomose mansoni/veterinária , Zoonoses/transmissão
19.
Ann N Y Acad Sci ; 1408(1): 79-89, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29239481

RESUMO

A reduction in the burden of schistosomiasis is potentially achievable by integrating a schistosomiasis vaccine with current control measures. Here, we determine parasite-specific in vitro responses of B, T, and NK cells from naive uninfected rhesus macaques to Schistosoma mansoni (Sm) egg (SmEA) and worm antigen (SmWA) preparations isolated from infected baboons. Pronounced B cell responses to SmEA and NK cell responses to both SmEA and SmWA were observed. High levels of IL-2 and IL-21 responses against Sm antigens were observed in T and non-T cells of lymph nodes (LNs) and gut lamina propria-derived lymphocytes (LPLs). Data analysis showed multifunctionality of LN-derived CD4+ , CD8+ , and CD4+ CD8+ double positive T cells against either SmWA or SmWA+SmEA antigen preparations. Distinct SmEA-specific multifunctional responses were observed in gut LPLs, suggesting simultaneous responses against egg antigens. These data provide insight into the immune effectors involved in schistosome responses by rhesus macaques.


Assuntos
Antígenos de Helmintos/imunologia , Doenças dos Macacos/imunologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/veterinária , Animais , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Interleucina-2/imunologia , Interleucina-2/metabolismo , Interleucinas/imunologia , Interleucinas/metabolismo , Células Matadoras Naturais/imunologia , Linfonodos/imunologia , Macaca mulatta , Doenças dos Macacos/parasitologia , Papio , Remissão Espontânea , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/parasitologia
20.
Am J Trop Med Hyg ; 95(4): 849-851, 2016 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-27503513

RESUMO

Schistosomiasis affects millions of people across Africa. We detected eggs of Schistosoma mansoni in western lowland gorilla and central chimpanzee fecal samples in Loango National Park, Gabon. We analyzed nuclear and mitochondrial DNA, namely internal transcribed spacer and cytochrome c oxidase subunit 1 fragments, and the resulting maximum likelihood phylogenetic analyses and haplotype network of the ITS and COI, respectively, showed that the samples from gorillas and chimpanzees clustered clearly within the S. mansoni clade. This is the first confirmed record of S. mansoni from Gabon, which urges surveillance in the area and prompts questions regarding the extent of zoonotic transmission and the clinical impact.


Assuntos
DNA Intergênico/genética , DNA Mitocondrial/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Schistosoma mansoni/genética , Esquistossomose mansoni/veterinária , Animais , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/veterinária , Fezes/parasitologia , Gabão/epidemiologia , Gorilla gorilla/parasitologia , Haplótipos , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/veterinária , Pan troglodytes/parasitologia , Filogenia , Subunidades Proteicas , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/epidemiologia , Análise de Sequência de DNA
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