BackgroundSchistosomiasis continues to be a significant public health problem. This disease affects 200 million people worldwide and almost 800 million people are at risk of acquiring the infection. Although vaccine development against this disease has experienced more failures than successes, encouraging results have recently been obtained using membrane-spanning protein antigens from the tegument of Schistosoma mansoni. Our group recently identified Sm29, another antigen that is present at the adult worm tegument surface. In this study, we investigated murine cellular immune responses to recombinant (r) Sm29 and tested this protein as a vaccine candidate.Methods and FindingsWe first show that Sm29 is located on the surface of adult worms and lung-stage schistosomula through confocal microscopy. Next, immunization of mice with rSm29 engendered 51%, 60% and 50% reduction in adult worm burdens, in intestinal eggs and in liver granuloma counts, respectively (p<0.05). Protective immunity in mice was associated with high titers of specific anti-Sm29 IgG1 and IgG2a and elevated production of IFN-γ, TNF-α and IL-12, a typical Th1 response. Gene expression analysis of worms recovered from rSm29 vaccinated mice relative to worms from control mice revealed a significant (q<0.01) down-regulation of 495 genes and up-regulation of only 22 genes. Among down-regulated genes, many of them encode surface antigens and proteins associated with immune signals, suggesting that under immune attack schistosomes reduce the expression of critical surface proteins.ConclusionThis study demonstrates that Sm29 surface protein is a new vaccine candidate against schistosomiasis and suggests that Sm29 vaccination associated with other protective critical surface antigens is the next logical strategy for improving protection.
Eight new species of Paravelia Breddin, 1898 from Brazil are described and illustrated: P. amapaensis sp. nov. from Amapá State, P. bipunctata sp. nov. from Minas Gerais, Mato Grosso and Mato Grosso do Sul States, P. bilobata sp. nov. and P. polhemusi sp. nov. from Mato Grosso State, P. bahiana sp. nov. from Bahia State, P. lacrymosa sp. nov. from Minas Gerais State, P. micromaculata sp. nov. from Maranhão State, and P. ornata sp. nov. from Amazonas State. The genus is redescribed, with photos of the dorsal view for nineteen species: P. basalis (Spinola), P. biae Spangler, P. boliviana Breddin, P. bullialata Polhemus & Polhemus, P. capillata (Drake& Harris), P. capixaba Moreira, Nessimian & Rúdio, P. conata (Hungerford), P. dilatata Polhemus & Polhemus, P. foveata Polhemus & Polhemus, P. itatiayana (Drake), P. lanemeloi Moreira & Barbosa, P. manausana Polhemus & Polhemus, P. nieseri Moreira & Barbosa, P. platensis (Berg), P. recens (Drake & Harris), P. rotundanotata (Hungerford), P. spinifera Polhemus & Polhemus, P. splendoris (Drake & Harris) and P. williamsi (Hungerford). Three of these species are recorded for the first time from Brazil: P. platensis, P. spinifera and P. williamsi. Also, the macropterous forms of P. capixaba and P. dilatata are described. Lastly, an identification key to the 36 species of Paravelia recorded from Brazil and a checklist of described species are presented.
The need for daily parenteral administration represents one of the most serious limitations in the clinical use of pentavalent antimonials against leishmaniasis. In this work, we investigated the ability of -cyclodextrin to enhance the oral absorption of antimony and to promote the oral efficacy of meglumine antimoniate against experimental cutaneous leishmaniasis. The occurrence of interactions between -cyclodextrin and meglumine antimoniate was demonstrated through the changes induced in the spin lattice relaxation times of protons in both compounds. When free and complexed meglumine antimoniate were given orally to Swiss mice, plasma antimony levels were found to be about three times higher for the meglumine antimoniate--cyclodextrin complex than for the free drug. Antileishmanial efficacy was evaluated in BALB/c mice experimentally infected with Leishmania amazonensis. Animals treated daily with the complex (32 mg of Sb/kg of body weight) by the oral route developed significantly smaller lesions than those treated with meglumine antimoniate (120 mg of Sb/kg) and control animals (treated with saline). The effectiveness of the complex given orally was equivalent to that of meglumine antimoniate given intraperitoneally at a twofold-higher antimony dose. The antileishmanial efficacy of the complex was confirmed by the significantly lower parasite load in the lesions of treated animals than in saline-treated controls. This work reports for the first time the effectiveness of an oral formulation for pentavalent antimonials.Pentavalent antimonials, including meglumine antimoniate, are the main drugs used in the treatment of all forms of leishmaniasis (1, 2, 9). These highly water-soluble compounds are considered inactive when given enterally and are subject to rapid renal clearance after parenteral administration, requiring a multiple-dosing regimen. Antimony (Sb) therapy is often accompanied by local pain during and just after intramuscular injections and by severe systemic side effects requiring very careful medical supervision. All these factors contribute to high cost and compliance difficulties that may ultimately lead to treatment failures. This also explains why so much effort is being devoted to the search for orally active antileishmanial drugs (4, 7, 13).The association of drugs with carrier systems is a feasible strategy to improve oral absorption. Among drug carrier systems, cyclodextrins, which are cyclic oligosaccharides composed of glucose units joined through ␣-1,4 glucosidic bonds, have been one of the most successful drug absorption enhancers for oral delivery (5, 14).We show here that -cyclodextrin forms a complex with meglumine antimoniate and report the impact of this association on the oral absorption of antimony in mice and on the efficacy of meglumine antimoniate in an experimental model of cutaneous leishmaniasis. The meglumine antimoniate--cyclodextrin complex was prepared by mixing -cyclodextrin and meglumine antimoniate in distilled water at a 1:1 cyclodextrin/Sb molar ratio, heati...
SUMMARYPleurolophocercous cercariae emerged from naturally infected Melanoides tuberculata from Minas Gerais State, Brazil, were used to perform experimental infection of laboratory-reared Poecilia reticulata. Mature metacercariae were obtained from the gills of fishes and force-fed to Mus musculus. The adult parasites which recovered from small intestines of mice were identified as Centrocestus formosanus. This is the first report of M. tuberculata as intermediate host of this heterophyid in Brazil. Despite some studies related to the interaction between M. tuberculata and planorbid molluscs which transmit Schistosoma mansoni Sambon, 1907 in the country 13,14 , the possible damage on the native fauna as alien species and their potential to act as parasite vector in the country have not yet been evaluated. In this later aspect, some studies had already reported the finding of M. tuberculata harboring pleurolophocercous cercariae in Brazil 5,6,39 , but these larvae, characterized as Pleurolophocercous type, still remain without a specific identification. KEYWORDS:In the present study, malacological surveys were performed at Pampulha dam (an artificial lake located between 43 0 58' and 44 0 01'W and 19 0 50' and 19 0 52'S, in the northern region of the city of Belo Horizonte and 2 km away from the campus of "Universidade Federal de Minas Gerais") from March 2006 to July 2009. Molluscs were collected with a scoop net and long forceps. After a preliminary trial, molluscs were placed in a thermal box, labeled and shipped to the laboratory. Then they were placed individually in plastic recipients containing 5 mL of tap water and left overnight at room temperature. Thiarids were examined with a stereomicroscope before and after artificial photostimulation for two hours. Emerged larvae were collected with micropipette, transferred to glass slides and analyzed with vital stains (0.05% neutral red, 0.05% toluidine blue, 0.05% alizarin red) or fixed and then stained with acetic carmine and mounted in Canada balsam 23 .Cercariae were concentrated by filtration using a Buchner funnel 31 and one hundred larvae in 5 mL were used for individual infection of 30 adult specimens (2-3 cm of length) of laboratory reared Poecilia reticulata Peters, 1859 (Pisces: Poeciliidae). Thirty days after infection the surviving fishes were necropsied in order to recover metacercariae. Cysts obtained from gills of experimentally infected fish were administered per os to five mice of the AKR/J strain. Fifteen days after infection, mice were sacrificed by cervical dislocation according to the local animal experimentation ethics committee (CETEA/UFMG), and their intestines were thoroughly and longitudinally opened in Petri dishes containing 0.85% saline solution and adult parasites were recovered from the proximal third of the small intestine. Parasites were studied alive or then placed between the slide and the coverslip with slight pressure, fixed in cold 10% formalin, stained with acetic carmine, dehydrated, cleared in benchwood and mounted in C...
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