Differential protective impact of peptide vaccine formulae targeting the lung- and liver-stage of challenge Schistosoma mansoni infection in mice.

The study aimed to elicit protective immune responses against murine schistosomiasis mansoni at the parasite lung- and liver stage. Two peptides showing amino acid sequence similarity to gut cysteine peptidases, which induce strong memory immune effectors in the liver, were combined with a peptide based on S. mansoni thioredoxin peroxidase (TPX), a prominent lung-stage schistosomula excretory-secretory product, and alum as adjuvant. Only one of the 2 cysteine peptidases-based peptides in a multiple antigenic peptide construct (MAP-3 and MAP-4) appeared to adjuvant protective immune responses induced by the TPX peptide in a MAP form. Production of TPX MAP-specific IgG1 serum antibodies, and increase in lung interleukin-1 (IL-1), uric acid, and reactive oxygen species (ROS) content were associated with significant (P < 0.05) 50 % reduction in recovery of lung-stage larvae. Increase in lung triglycerides and cholesterol levels appeared to provide the surviving worms with nutrients necessary for a stout double lipid bilayer barrier at the parasite-host interface. Surviving worms-released products elicited memory responses to the MAP-3 immunogen, including production of specific IgG1 antibodies and increase in liver IL-33 and ROS. Reduction in challenge worm burden recorded 45 days post infection did not exceed 48 % associated with no differences in parasite egg counts in the host liver and small intestine compared to unimmunized adjuvant control mice. Alum adjuvant assisted the second peptide, MAP-4, in production of IgG1, IgG2a, IgG2b and IgA specific antibodies and increase in liver ROS, but with no protective potential, raising doubt about the necessity of adjuvant addition. Accordingly, different vaccine formulas containing TPX MAP and 1, 2 or 3 cysteine peptidases-derived peptides with or without alum were used to immunize parallel groups of mice. Compared to unimmunized control mice, significant (P < 0.05 to < 0.005) 22 to 54 % reduction in worm burden was recorded in the different groups associated with insignificant changes in parasite egg output. The results together indicated that a schistosomiasis vaccine able to entirely prevent disease and halt its transmission still remains elusive.

Cerebral mansoni schistosomiasis: a systematic review of 33 cases published from 1989 to 2019.

BACKGROUND: We investigated the epidemiology, clinical presentation and outcomes of individuals affected by cerebral schistosomiasis. METHODS: This systematic review was planned in accordance with current guidelines for performing comprehensive systematic reviews and meta-analysis, including the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. RESULTS: Most of patients presented with seizures (48.5%), which is a non-specific symptom despite its high prevalence. There was no specific clinical manifestation that could help the diagnosis, which was made in 69.7% by histopathological analysis of brain tissue. CONCLUSIONS: Seizures are a non-specific symptom to diagnose patients with cerebral schistosomiasis and accurate clinical indicators need to be derived through further studies.

Barbatic acid from Cladia aggregata (lichen): Cytotoxicity and in vitro schistosomicidal evaluation and ultrastructural analysis against adult worms of Schistosoma mansoni.

Schistosomiasis is one of the most significant neglected tropical diseases, affecting around 260 million people worldwide, and Praziquantel is currently the only available drug for the treatment of infected persons. Thus, the search for new schistosomicidal compounds is urgent. The objective of this study was to investigate of the schistosomicidal effect of barbatic acid, a lichen metabolite, on adult worms of Schistosoma mansoni. The in vitro schistosomicidal effect was evaluated through the assessment of motility and mortality, cellular viability of the worms and ultrastructural analysis through scanning electron microscopy. To evaluate the cytotoxicity of barbatic acid, a cell viability assay was performed with human peripheral blood mononuclear cells. Barbatic acid showed a schistosomicidal effect after 3 h of exposure. At the end of 24 h the concentrations of 50-200 µM presented lethality on the worms. Motility changes were observed at sublethal concentrations. The IC50 obtained by the cell viability assay for S. mansoni was 99.43 µM. Extensive damage to the worm's tegument was observed from 25 µM. No cytotoxicity was observed on human peripheral blood mononuclear cells. This report provides data showing the schistosomicidal effect of barbatic acid on S. mansoni, causing death, motility changes and ultrastructural damage to worms. In addition, barbatic acid was shown to be non-toxic to human peripheral blood mononuclear cells at concentrations that are effective against S. mansoni.

Potassium usnate toxicity against embryonic stages of the snail Biomphalaria glabrata and Schistosoma mansoni cercariae.

The snail Biomphalaria glabrata is the most important vector for Schistosoma mansoni. Control of this vector to prevent the spread of schistosomiasis is currently performed with the application of a niclosamide molluscicide, which is highly toxic to the environment. Screening of substances that show embryotoxic molluscicidal potential as well as have detrimental effects on cercariae is very relevant for the control of schistosomiasis, as the efficacy of prevention of the disease is increased if it acts as a molluscicide as well as on the cercariae of S. mansoni. The aim of this work was to evaluate the effect of potassium usnate derived from usnic acid on different stages of embryonic development of B. glabrata and on S. mansoni cercariae. After 24 h of exposure, potassium usnate showed embryotoxic activity across all embryonic stages. The values obtained from the LC50 for the embryonic stages were the following: blastula 5.22 µg/mL, gastrula 3.21 µg/mL, trochophore 3.58 µg/mL, veliger 2.79, and hippo stage 2.52 µg/mL. Against S. mansoni cercariae, it had LC90 and 100% mortality at concentrations of 2.5 and 5 µg/mL in 2 h of exposure. In conclusion, this is the first report of potassium usnate toxicity on the embryonic stages of B. glabrata and cercariae of S. mansoni, and this study shows the potassium usnate as a promising agent for the control of mansoni schistosomiasis.

Alterações angiográficas e pressóricas determinadas pela esplenectomia e ligadura da veia gástrica esquerda em portadores de esquistossomose mansônica / Angiografic and pressoric changes determined by splenectomy with left gastric vein ligature in mansoni schistosomiasis

RACIONAL: Na esquistossomose mansônica na forma hepatoesplênica ocorre fibrose hepática difusa que associada à congestão venosa do sistema porta resulta em hepatoesplenomegalia. Pode produzir hemorragia digestiva alta por rotura das varizes de esôfago e do estômago ou lesões pépticas da mucosa gastroduodenal. OBJETIVO: Estudar os efeitos da esplenectomia e ligadura da veia gástrica esquerda sobre a hemodinâmica portohepática. MÉTODO: Vinte e três portadores de esquistossomose mansônica na forma hepatoesplênica foram estudados prospectivamente, antes e cerca de duas semanas após a operação, através de estudos angiográficos dos diâmetros da artéria hepática comum e própria, artéria esplênica, artéria mesentérica superior, veia porta, veia mesentérica superior e veia gástrica esquerda. Foram aferidas as pressões da veia cava inferior, venosa central, da veia hepática livre, da veia hepática ocluída e sinusoidal. RESULTADOS: A ligadura da veia gástrica esquerda determinou acréscimo significante nas seguintes variáveis: diâmetros da artéria hepática comum e própria; diâmetro da veia mesentérica superior; o acréscimo não foi significante nas seguintes medidas: pressão venosa central e diâmetro da artéria mesentérica superior. Ela promoveu decréscimo não significante nas variáveis: pressão da veia cava inferior; pressão da veia hepática livre; pressão da veia hepática ocluída; pressão sinusoidal; diâmetro da veia porta. CONCLUSÃO: A ligadura da veia gástrica esquerda, na maioria dos casos, não determina alterações hemodinâmicas significantes do sistema porta capazes de quebrar o equilíbrio hemodinâmico funcional, que caracteriza a esquistossomose mansônica na forma hepatoesplênica.

BACKGROUND: In hepatosplenic schistosomiasis occurs diffuse hepatic fibrosis associated with venous congestion of the portal system resulting in hepatosplenomegaly. It can produce digestive hemorrhage caused by rupture of esophageal and stomach varices or peptic gastroduodenal mucosal lesions. AIM: To study the effects of splenectomy and ligature of the left gastric vein on portohepatic hemodynamics. METHOD: Twenty-three patients with hepatosplenic schistosomiasis mansoni were studied before and about two weeks after operation through angiographic diameter of the common and proper hepatic artery, splenic artery, superior mesenteric artery, portal vein, superior mesenteric vein and left gastric vein. The pressures of the inferior vena cava and central venous pressure, free hepatic vein, the hepatic sinusoidal and occluded vein were measured. RESULTS: The splenectomy and ligature of the left gastric vein determined low morbidity and null mortality. It determined significant addition to the following variables: diameters of the common and proper hepatic artery; diameter of the superior mesenteric vein. It determined non significant increase on the following measurements: right atrial pressure and diameter of the superior mesenteric artery. It determined non significant decrease to the following variables: inferior vena cava pressure; free hepatic vein pressure; occluded hepatic vein pressure; sinusoidal pressure, diameter of the portal vein. CONCLUSION: Splenectomy and ligature of the left gastric vein do not determine portal hemodynamic changes capable of breaking the functional hemodinamic balance that characterizes the hepatosplenic mansoni schistosomiasis.

Endomyocardial fibrosis associated with mansoni schistosomiasis / Endomiocardiofibrose associada à esquistossomose mansoni

Endomyocardial fibrosis (EMF) is a neglected tropical disease that affects millions of people worldwide. EMF is the most common cause of restrictive cardiomyopathy, caused by deposition of fibrous tissue on endocardial surfaces. EMF is a major cause of death in areas where it is endemic, but the pathogenesis of the disease is poorly understood. Schistosomiasis mansoni is a parasitic disease endemic in Brazil, where EMF has also been described. The association between EMF and schistosomiasis has been suggested in various publications, seeking a possible correlation between endocardial and periportal fibroses. This report describes a case of EMF associated with schistosomiasis.

A endomiocardiofibrose (EMF) é uma doença tropical, negligenciada, que afeta milhões de pessoas no mundo. É considerada a causa mais comum de cardiomiopatia restritiva, causada pela deposição de tecido fibroso em superfícies endocárdicas. Endomiocardiofibrose é uma das principais causas de morte em áreas onde é endêmica, e sua patogênese é pouco conhecida. A esquistossomose mansoni é uma doença parasitária endêmica no Brasil, onde a EMF também tem sido descrita. Tem sido apontada associação entre EMF e esquistossomose em várias publicações, buscando-se uma possível correlação entre a fibrose endocárdica e periportal. Neste relato, descreve-se um caso de EMF associado a esquistossomose.

Participação das plaquetas no processo de fibrose dos pacientes com esquistossomose mansônica / Participation of platelets in the process of fibrosis in patients with mansonic schistosomiasis

O objetivo deste estudo foi avaliar a ativação plaquetária através da P-selectina e o conteúdo de PDGF-AB e TGFbeta1, nos pacientes com esquistossomose que desenvolveram fibrose (F3), naqueles que não tiveram esta manifestação (F0) e nos controles (C). Os resultados mostraram que a percentagem de P-selectina nas plaquetas sem estímulo de agonistas foi de 10,6 por cento nos F3; 11,1 por cento nos FO, e 6,3 por cento nos C e após a adição de ADP/adrenalina, foi de 44 por cento; 25,3 por cento e 42 por cento, respectivamente. A dosagem do PDGF-AB e TGFbeta1 por plaquetas foi de 11,016ng/dL (F3); 3,172 ng/dL (F0) e 5,01ng/dL (C) e, (0,012ng/dL (F3); 5,27ng/dL (F0) e 4,66ng/dL (C), respectivamente. Em relação à P-selectina, concluímos que as plaquetas dos pacientes com esquistossomoses, apesar de estarem pré ativadas, mantiveram-se responsivas aos agonistas. O TFGbeta1 não apresentou diferença entre os três grupos, enquanto o PDGF-AB foi significantemente maior no grupo F3, sugerindo a participação deste no desenvolvimento da fibrose.

The aim of this study was to evaluate platelet activation through P-selectin, and PDGF-AB and TGFbeta1 content, in schistosomiasis patients who developed fibrosis (F3) and who did not present this (F0), and in a control group (C). The results showed that the percentage of P-selectin in platelets without agonist stimulation was 10.6 percent in F3, 11.1 percent in F0 and 6.3 percent in C. After the addition of ADP/adrenaline, the percentages were 44 percent, 25.3 percent and 42 percent, respectively. The PDGF-AB and TGFbeta1 contents per platelet were 11,016ng/dl (F3), 3,172ng/dl (F0) and 5.01ng/dl (C) and 0,012ng/dl (F3), 5.27ng/dl (F0) and 4.66ng/dl (C), respectively. Concerning the P-selectin, we can conclude that platelets from patients with schistosomiasis continued to be responsive to agonists, despite being pre-activated. There were no differences in TGFbeta1 between the groups, but the PDGF-AB content was significantly higher in F3. This suggests that PDGF-AB may have some participation in the development of fibrosis.

Esquistossomose mansônica em vesícula seminal / Schistosomiasis mansoni in the seminal vesicle

Em regiões endêmicas, a esquistossomose mansônica é responsável por uma alta taxa de morbimortalidade por doenças associadas à infestação do sistema hepático. O acometimento genital pela schistosomiasis mansoni é raro. Nós relatamos o primeiro caso de esquistossomose mansônica em vesícula seminal diagnosticado, incidentalmente, pelo exame histopatológico da próstata e vesículas seminais removidos cirurgicamente.

In endemic regions, Mansoni schistosomiasis is responsible for high morbidity-mortality rates due to diseases associated with infestation of the hepatic system. Genital involvement caused by Mansoni schistosomiasis is rare. We report the first case of Mansoni schistosomiasis in the seminal vesicle, which was diagnosed incidentally by means of histopathological study of the prostate and seminal vesicles after surgical removal.