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In this study, Licochalcone A (LicoA) was investigated in in vitro and in vivo assays. The survival of worms in culture, the pattern of oviposition, the count of intact tubers and the integrity of the coat were adopted in the in vitro tests. After the animals were perfused, the number of worms recovered, their location and the oogram study were the parameters analyzed to signal the existence of potential schistosomicidal activity in vivo. We observed reduction on the survival, integument integrity and reproduction of adult worms in vitro. Murine models did not show a significant difference in the parasitological parameters analyzed that indicate activity against the worms with an oral single dose of 25 mg/ kg of LicoA or two intraperitoneal injection of 50 mg/ kg LicoA. Nevertheless, it is too early to completely exclude the schistosomicide activity of LicoA, considering that the used dosage form could not provide a regular absorption of the drug.

BACKGROUND Angiostrongylus cantonensis is the etiological agent of neuroangiostrongyliasis in humans, which is developed in gastropods and vertebrate species, mainly rodents. Human transmission occurs through consumption of molluscs and paratenic hosts infected with L3, and the migration of larvae to the central nervous system causes eosinophilic meningitis. Laboratory diagnosis is based on molecular and immunological tests, using young or adult females as a source of antigens. However, these tests give positive results only after several weeks of symptoms onset and also cross-reactions with others parasite infections may occur. OBJECTIVES The purpose of this work was to study different antigenic preparations of distinct evolutionary phases of A. cantonensis, in order to improve serological techniques for disease immunodiagnosis. METHODS For this purpose, antigenic fractions of different evolutionary forms were evaluated by Dot-enzyme-linked immunosorbent assay (Dot-ELISA) and Western blot using serum samples. FINDINGS All analysed fractions showed reactivity with serum samples from patients with neuroangiostrongyliasis, especially female membrane alkaline (FAM) and female soluble alkaline (FAS) fractions together with female soluble saline (FSS), improving the technique specificity. MAIN CONCLUSIONS The results point to the possibility of use of raw female antigens in association with alkaline membrane antigens extracted from adult worms to aid in diagnosis and helps initiate neuroangiostrongyliasis surveillance and control actions.

Several studies described the effect of human TNF-α on Schistosoma mansoni. It affects the worm’s development, metabolism, egg-laying, changes in the parasite´s gene expression and protein phosphorylation. Data available concerning the influence of hTNF-α on egg-laying are controversial and understanding the mechanism of egg-laying regulation is essential in combating schistosomiasis. We characterized the effects of in vitro treatment of S. mansoni adult worms with different doses of hTNF-α (5, 20 and 40ng/mL) for five days. We explored the effects on the egg-laying rate, glucose, ATP metabolism, mRNA expression levels of lactate dehydrogenase, of glucose transporters and of SmTNFR, the parasite gene for hTNF-α receptor. hTNF-α influenced egg-laying in a time and dose dependent manner: with 40ng/mL, egg-laying increased on day 2 and decreased on days 3 and 4; 20 ng/mL dose, egg-laying decreased on day 3, while at 5ng/mL dose, egg-laying decreased on day 4. The total number of eggs produced was not affected, but the egg-laying dynamic was altered; the median egg-laying time decreased significantly due to treatment. At 5 and 20ng/mL hTNF-alpha, lactate production diminished on days 3 up to 5, while glucose uptake increased on day 5. At 40ng/mL, glucose uptake diminished on days 1 up to 3, while ATP accumulation was detected on day 5. No significant changes in the mRNA expression were detected in all treatments. Crosstalk involving the hTNF-alpha and the parasite signaling play a role in the fine regulation of the worm´s metabolism and physiology and points to new strategies for disease control.

Several studies have described the effects of human tumor necrosis factor alpha (hTNF-α) on Schistosoma mansoni. hTNF-α affects the worm’s development, metabolism, egg-laying, gene expression and protein phosphorylation. The available data on the influence of hTNF-α on egg-laying in S. mansoni are controversial, but understanding the mechanism of egg-laying regulation in this species is essential in combating schistosomiasis. We characterized the effects of in vitro treatment of S. mansoni adult worms with different doses of hTNF-α (5, 20 and 40 ng/ml) for 5 days. We explored the effects on egg-laying rate, glucose levels, ATP metabolism, and messenger RNA (mRNA) expression levels of lactate dehydrogenase, glucose transporters and the parasite gene which acts as an hTNF-α receptor, SmTNFR. hTNF-α influenced egg-laying in a time- and dose-dependent manner: at a dose of 40 ng/ml, egg-laying increased on day 2 and decreased on days 3 and 4; at 20 ng/ml, egg-laying decreased on day 3; while at 5 ng/ml, egg-laying decreased on day 4. The total number of eggs produced was not affected by the different treatments, but the egg-laying dynamics were: the median egg-laying time decreased significantly with treatment, and egg developmental stages and size were also affected. At 5 and 20 ng/ml hTNF-α, lactate production diminished on day 3 up to day 5, while glucose uptake increased on day 5. At 40 ng/ml, glucose uptake diminished on day 1 up to day 3, while ATP accumulation was detected on day 5. No significant changes in mRNA expression were detected in any of the treatments. We found that crosstalk involving hTNF-α and parasite signaling plays a role in the fine-scale regulation of the worm’s metabolism and physiology, and points to new strategies for disease control. Graphical abstract

Background Intestinal parasitic infections (IPIs) are caused by several species of protozoa and helminths and are among the most frequent infections in many regions of the world, particularly in countries with limited access to adequate conditions of hygiene and basic sanitation, and have significant morbidity. There are few studies that assess the prevalence of intestinal parasites in Latin America. We investigated the prevalence of intestinal infections in five neighborhoods in the city of Barra Mansa / RJ / Brazil. Objective To evaluate the prevalence of geohelminths, protozoa and Schistossoma mansoni infection, using two parasitological methods in a population in a city in the state of Rio de Janeiro (Brazil). Methods Cross-sectional cohort study, conducted from September 2010 to April 2011, in individuals over five years old, to assess the prevalence of IPIs in 5 peripheral neighborhoods of Barra Mansa, a city located in the state of Rio de Janeiro (Brazil): Siderlândia, Cantagalo, São Luiz, Nova Esperança and Santa Clara, through the combination of two parasitological methods, Kato-Katz and Hoffman, having analyzed a total of six slides for each of the research participants. Results Results of samples from 610 individuals were collected and analyzed using the Kato-Katz (KK) and Hoffman (HH) methods. Approximately 60% of the individuals were female, with an average age of 39.72 years. Five hundred and fifty-one (84.8%) had access to treated water and 486 (74.8%) to the sewage network. The neighborhood of Siderlândia contributed most of the casuistry (42.9%). About 4% of participants reported a previous history of schistosomiasis. Six hundred and ten stool samples were evaluated using the Kato-Katz and Hoffmann methods. The results of parasitological examinations by the KK method showed low positivity for any diagnosed parasitosis. The HH method showed a more significant number of parasitic infections, with a higher frequency of Endolimax nana (17.4%), followed by Blastocystis spp (10.8%). The positivity in stool tests using the KK or HH methods was significantly higher in the Santa Clara neighborhood (p = 0.038), in people who use river water (p Conclusions The use of two stool samples examined by the KK and HH methods improved the detection sensitivity and evidenced the low prevalence of IPIs in the city of Barra Mansa (RJ) / Brazil.

The nematode Angiostrongylus cantonensis is the most common cause of neuroangiostrongyliasis (manifested as eosinophilic meningitis) in humans. Gastropod molluscs are used as intermediate hosts and rats of various species are definitive hosts of this parasite. In this study, we identified several environmental factors associated with the presence and abundance of terrestrial gastropods in an impoverished urban region in Brazil. We also found that body condition, age and presence of co-infection with other parasite species in urban Rattus norvegicus, as well as environmental factors were associated with the probability and intensity of A. cantonensis infection. The study area was also found to have a moderate prevalence of the nematode in rodents (33% of 168 individuals). Eight species of molluscs (577 individuals) were identified, four of which were positive for A. cantonensis. Our study indicates that the environmental conditions of poor urban areas (presence of running and standing water, sewage, humidity and accumulated rain and accumulation of construction materials) influenced both the distribution and abundance of terrestrial gastropods, as well as infected rats, contributing to the maintenance of the A. cantonensis transmission cycle in the area. Besides neuroangiostrongyliasis, the presence of these hosts may also contribute to susceptibility to other zoonoses.

BackgroundSchistosomiasis is a socioeconomically devastating parasitic infection afflicting hundreds of millions of people and animals worldwide. It is the most important helminth infection, and its treatment relies solely on the drug praziquantel. Oral H1-antihistamines are available worldwide, and these agents are among the most widely used of all medications in children and adults. Given the importance of the drug repositioning strategy, we evaluated the antischistosomal properties of the H1-antihistamine drugs commonly used in clinical practices.MethodsTwenty-one antihistamine drugs were initially screened against adult schistosomesex vivo. Subsequently, we investigated the anthelmintic properties of these antihistamines in a murine model of schistosomiasis for both early and chronicS. mansoniinfections at oral dosages of 400 mg/kg single dose or 100 mg/kg daily for five consecutive days. We also demonstrated and described the ability of three antihistamines to induce tegumental damage in schistosomes through the use of scanning electron microscopy.ResultsFrom phenotypic screening, we found that desloratadine, rupatadine, promethazine, and cinnarizine kill adultS. mansoni in vitroat low concentrations (5–15 µM). These results were further supported by scanning electron microscopy analysis. In an animal model, rupatadine and cinnarizine revealed moderate worm burden reductions in mice harboring either early or chronicS. mansoniinfection. Egg production, a key mechanism for both transmission and pathogenesis, was also markedly inhibited by rupatadine and cinnarizine, and a significant reduction in hepatomegaly and splenomegaly was recorded. Although less effective, desloratadine also revealed significant activity against the adult and juvenile parasites.ConclusionsAlthough the worm burden reductions achieved are all only moderate, comparatively, treatment with any of the three antihistamines is more effective in early infection than praziquantel. On the other hand, the clinical use of H1-antihistamines for the treatment of schistosomiasis is highly unlikely.

Oxazine derivatives, a class of heterocyclic compounds, exhibit a variety of biological properties, such as anticonvulsant and antitumor activities. In this study, we evaluated the effect of two cyclohexene-fused 1,3-oxazines (cis‑1-benzyl-N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (1) and trans‑N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (2)) in cultures of Bacillus cereus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Serratia marcescens, Shigella flexneri and Staphylococcus aureus by the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). Additionally, the ex vivo antiparasitic activity of oxazines was assessed against Schistosoma mansoni, a helminth that is one of the major agents of the disease schistosomiasis Also, oxazines were evaluated on three tumor cell lines, NCI-H292 (human lung carcinoma), MCF-7 (human breast adenocarcinoma) and HEp-2 (human cervix carcinoma), and two normal cell lines (Vero and red blood cells). Bioassays revealed that oxazine 2 is more effective against bacteria than oxazine 1, with the lowest MIC and MBC values of 3.91 and 32.5 μg/mL, respectively. Similarly, compound 2 demonstrated higher antiparasitic activity than 1, and scanning electron microscopy analysis showed several morphological alterations in the tegument of worms in a concentration-dependent manner. In contrast, both oxazines exhibited low cytotoxic effects on cancer and normal cell lines. These results indicated that oxazines exerted direct effects on bacteria and parasite schistosomes. More importantly, since schistosomiasis control programs rely on one drug, praziquantel, oxazines may have the potential to become new antischistosomal agents. Fil: de Brito, Maria R.M.. Federal University of Piauí; Brasil Fil: Peláez, Walter José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Faillace, Martín Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Militão, Gardenia C.G.. Federal University of Pernambuco; Brasil Fil: Almeida, Jackson R.G.S.. Federal University Of San Francisco Valley; Brasil Fil: Argüello, Gustavo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Szakonyi, Zsolt. University of Szeged; Hungría Fil: Fülöp, Ferenc. University of Szeged; Hungría Fil: Salvadori, Maria C.. Universidade de Sao Paulo; Brasil Fil: Teixeira, Fernanda S.. Universidade de Sao Paulo; Brasil Fil: Freitas, Rivelilson M.. Federal University of Piauí; Brasil Fil: Pinto, Pedro L.S.. Instituto Adolfo Lutz; Brasil Fil: Mengarda, Ana C.. Universidade Guarulhos; Brasil Fil: Silva, Marcos P.N.. Universidade Guarulhos; Brasil Fil: Da Silva Filho, Ademar A.. Universidade Federal de Juiz de Fora; Brasil Fil: de Moraes, Josué. Universidade Guarulhos; Brasil

Schistosomiasis is a major public health problem worldwide, especially in poor communities. Since praziquantel is currently the only drug available to treat schistosomiasis, there is an urgent need to identify new antischistosomal drugs. Nerolidol is a sesquiterpene present as an essential oil in several plants that has been approved by the FDA. This study evaluated the in vivo antischistosomal activity of nerolidol in a mouse model of schistosomiasis infected with either adult or juvenile stages of Schistosoma mansoni. A single dose of nerolidol (100, 200 or 400 mg/kg) administered orally to mice infected with adult schistosomes resulted in a reduction in worm burden and egg production. Treatment with the highest nerolidol dose (400 mg/kg) caused significant reduction in a total worm burden of 70.06% (P 0.001). Additionally, the technique of quantitative and qualitative oograms showed that a single 400 mg/kg nerolidol dose achieved an immature egg reduction of 84.6% (P 0.001). In faecal samples, the Kato-Katz method also revealed a reduction of 75.2% in eggs/g at a dose of 400 mg/kg (P 0.001). Furthermore, scanning electron microscopy revealed that nerolidol-mediated worm killing was associated with tegumental damage. In contrast to activity against adult S. mansoni infection, oral treatment with nerolidol 400 mg/kg had low efficacy in mice harbouring juvenile schistosomes. Since nerolidol is already in use globally as a food additive and has a proven safety record, evaluation of this natural compound's potential for treatment of schistosomiasis could be entirely cost effective in the near future.

Pilocarpus microphyllus Stapf ex Wardlew (Rutaceae), popularly known as jaborandi, is a plant native to the northern and northeastern macroregions of Brazil. Several alkaloids from this species have been isolated. There are few reports of antibacterial and anthelmintic activities for these compounds. In this work, we report the antibacterial and anthelmintic activity of five alkaloids found in P. microphyllus leaves, namely, pilosine, epiisopilosine, isopilosine, epiisopiloturine and macaubine. Of these, only anthelmintic activity of one of the compounds has been previously reported. Nuclear magnetic resonance, HPLC and mass spectrometry were combined and used to identify and confirm the structure of the five compounds. As regards the anthelmintic activity, the alkaloids were studied using in vitro assays to evaluate survival time and damaged teguments for Schistosoma mansoni adult worms. We found epiisopilosine to have anthelmintic activity at very low concentrations (3.125 μg mL-1 ); at this concentration, it prevented mating, oviposition, reducing motor activity and altered the tegument of these worms. In contrast, none of the alkaloids showed antibacterial activity. Additionally, alkaloids displayed no cytotoxic effect on vero cells. The potent anthelmintic activity of epiisopilosine indicates the potential of this natural compound as an antiparasitic agent. Copyright © 2017 John Wiley & Sons, Ltd.

The treatment and control of schistosomiasis, a neglected disease that affects more than 200 million people worldwide, rely on the use of a single drug, praziquantel. A vaccine has yet to be developed, and since new drug design and development is a lengthy and costly process, drug repurposing is a promising strategy. In this study, the efficacy of promethazine, a first-generation antihistamine, was evaluated against Schistosoma mansoni ex vivo and in a murine model of schistosomiasis. In vitro assays demonstrated that promethazine affected parasite motility and viability, and it induced severe tegumental damage in schistosomes. The 50% lethal concentration (LC(50)) of the drug was 5.84 μM. Similar to promethazine, schistosomes incubated with atropine, a classical anticholinergic drug, displayed reduced motor activity. In an animal model, promethazine treatment was introduced at an oral dose of 100 mg/kg of body weight for five successive days at different intervals from the time of infection for the evaluation of the stage-specific susceptibility (prepatent and patent infections). Various parasitological criteria indicated the following in vivo antischistosomal effects of promethazine: there were significant reductions in worm burden, egg production, hepatomegaly, and splenomegaly. The highest worm burden reduction was achieved with promethazine in patent infections (>90%). Taken together, considering the importance of the repositioning of drugs in infectious diseases, especially those related to poverty, our data revealed the possibility of promethazine repositioning as an antischistosomal agent.

Background Treatment and control of schistosomiasis, one of the most insidious and serious parasitic diseases, depend almost entirely on a single drug, praziquantel. Since the funding for drug development for poverty-associated diseases is very limited, drug repurposing is a promising strategy. In this study, 73 nonsteroidal anti-inflammatory drugs (NSAIDs) commonly used in medical and veterinary fields were evaluated for their anti-schistosomal properties. Methods The efficacy of NSAIDs was first tested against adult Schistosoma mansoni ex vivo using phenotypic screening strategy, effective drugs were further tested in a murine model of schistosomiasis. The disease parameters measured were worm and egg burden, hepato- and splenomegaly. Findings From 73 NSAIDs, five (mefenamic acid, tolfenamic acid, meclofenamic acid, celecoxib, and diclofenac) were identified to effectively kill schistosomes. These results were further supported by scanning electron microscopy analysis. In addition, the octanol-water partition coefficient, both for neutral and ionized species, revealed to be a critical property for the ex vivo activity profile. Compounds were then tested in vivo using both patent and a prepatent S. mansoni infection in a mouse model. The most effective NSAID was mefenamic acid, which highly reduced worm burden, egg production, and hepato- and splenomegaly. Interpretation The treatment regimen used in this study is within the range for which mefenamic acid has been used in clinical practice, thus, it is demonstrated the capacity of mefenamic acid to act as a potent anti-schistosomal agent suitable for clinical repurposing in the treatment of schistosomiasis.

Schistosomiasis is a parasitic flatworm disease that infects over 200 million people worldwide, especially in poor communities. Treatment and control of the disease rely on just one drug, praziquantel. Since funding for drug development for poverty-associated diseases is very limited, drug repurposing is a promising strategy. In this study, from a screening of 13 marketed diuretics, we identified that spironolactone, a potassium-sparing diuretic, had potent antischistosomal effects on Schistosoma mansoni in vitro and in vivo in a murine model of schistosomiasis. In vitro, spironolactone at low concentrations (

Background:Systemic Sclerosis (SSc) is a chronic disease with multi-organ manifestations that may contribute to disability and low quality of life.1 Therefore, anxiety and depression are more frequent in SSc patients than in general population.2Objectives:To assess the prevalence of anxiety and depression in a SSc cohort and to evaluate its correlation with function, quality of life and assessment of gastrointestinal (GI) involvement scores.Methods:A cross-sectional study was conducted evaluating a cohort of SSc patients. All patients answered to the Hospital Anxiety and Depression Scale (HADS) questionnaire. A cut-off score < 8 was considered normal. Health Assessment Questionnaire (HAQ), Scleroderma HAQ (SHAQ), 36-Item Short Form Health Survey (SF-36), EuroQol-5D (EQ-5D) and University Of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Scale (UCLA SCTC GIT) 2.0 questionnaires were also obtained. Clinical data was obtained and analyzed.Results:We included 20 patients, 17 females [n = 17 (85%)], median (min, max) age was 52.5 (28, 75) years-old. Regarding disease classification, 13 (65%) had limited SSc, 4 (20%) had diffuse SSc and 3 (15%) had early SSc. A score ≥ 8 was found in 14 (70%) patients on HADS-A [median (min, max) = 9 (2, 19)] and in 12 (60%) patients on HADS-D [median (min, max) = 8 (1, 15)]. Depressive patients had significantly worst scores on the measures of function, such as HAQ and lung and gastrointestinal involvements and patient global assessment of SHAQ, of quality of life, such as EQ-5D and physical functioning, role physical, bodily pain, vitality, social functioning and mental health domains of SF-36, and on the UCLA SCTC GIT 2.0 scale. Anxious patients had significantly worst scores on social functioning and mental health domains of SF-36 and on the UCLA SCTC GIT 2.0 scale (Table 1).Conclusion:The prevalence of depression and anxiety on SSc patients is high and should not be neglected. Overall disability and multiorgan manifestations, particularly GI involvement, may contribute to a low quality of life and consequently to depression and anxiety.References:[1]Firestein & Kelley’s Textbook of Rheumatology 2-Volume Set, 11th Edition[2]Brett D. Thombs et al. Depression in Patients With Systemic Sclerosis: A Systematic Review of the Evidence. Arthritis & Rheumatism (Arthritis Care & Research) Vol. 57, 2007, pp 1089–1097Table 1.Function, quality of life and gastrointestinal (GI) involvement assessment according to HADS score.Results, median [min, max]HADS-D ≥ 8 (n = 12)HADS-D < 8 (n = 8)P-valueHADS-A ≥ 8 (n = 14)HADS-A < 8 (n = 6)P-valueSHAQ- GI involvement26.5 [0, 90]2 [0, 40]0.00918.5 [0, 90]2.5 [0, 40]0.091- Lung involvement48.5 [5, 90]2.5 [0, 30]0.00118 [0, 90]3 [0, 65]0.126- Patient global assessment67.5 [30, 100]4 [0, 85]0.01153.5 [2, 100]41.5 [0, 85]0.509HAQ1.375 [0.5, 2]0.1875 [0, 1]0.0011.25 [0, 2]0.875 [0, 1.125]0.147EQ5D0.3667 [-0.0573, 0.6937]0.6752 [0.2870, 1]0.0060.4640 [-0.0573, 0.7667]0.6752 [0.287, 1]0.075SF36- Physical functioning25 [15, 75]75 [50, 100]0.00140 [15, 100]72.5 [25, 85]0.106- Role physical31.25 [0, 75]72.875 [31.25, 100]0.02537.5 [0, 100]65.625 [31.25, 100]0.214- Bodily pain41 [0, 74]68 [20, 88]0.01141 [0, 88]61.5 [20, 74]0.428- Vitality25 [0, 43.75]65.625 [25, 75]0.00137.5 [0, 75]65.625 [12.5, 75]0.135- Social functioning37.5 [12.5, 87.5]87.5 [50, 100]0.00250 [12.5, 100]87.5 [87.5, 100]0.003- Mental health45 [25, 80]65.7 [51.4, 85]0.01245 [25, 75]77.5 [51.4, 85]0.005UCLA SCTC GIT 2.0- Reflux0.38 [0, 1.25]0 [0, 1.25]0.0240.25 [0, 1.25]0 [0, 1]0.139- Distension1 [0.5, 2]0.25 [0, 1.5]0.0171 [0.25, 2]0.125 [0, 1]0.024- Total0.44[0.1, 0.99]0.04 [0, 0.97]0.0100.34 [0.04, 0.99]0.02 [0, 0.44]0.018Disclosure of Interests:None declared

Background:Fatigue is a frequent and commonly undervalued symptom among rheumatic disease, including Systemic Sclerosis (SSc).1,2Objectives:To determine the prevalence of severe fatigue in a SSc cohort and to evaluate how it correlates with disability, quality of life and mental illness.Methods:A cross-sectional study was conducted evaluating a cohort of SSc patients. Fatigue was evaluated using Functional Assessment Chronic Illness Therapy (Fatigue) (FACIT-F) questionnaire. A value < 30 was defined as severe fatigue. Health Assessment Questionnaire (HAQ), Scleroderma HAQ (SHAQ), 36-Item Short Form Health Survey (SF-36), EuroQol-5D (EQ-5D) and Hospital Anxiety and Depression Scale (HADS) questionnaires were also filled. Clinical data was obtained and analysed.Results:We included 20 patients, 17 females [n = 17 (85%)], median (min, max) age was 52.5 (28, 75) years-old. Regarding disease classification, 13 (65%) had limited SSc, 4 (20%) had diffuse SSc and 3 (15%) had early SSc. The median FACIT-F score was 34 (3, 48). The prevalence of severe fatigue was 40% (n = 8). Fatigue had a moderate negative correlation with HAQ (τ = -0.641; p < 0.001) and a weak negative correlation with lung (τ = -0.345; p = 0.039) and gastrointestinal (τ = -0.419; p = 0.011) involvements and with patient global assessment (τ = -0.325; p = 0.047) subtopics of SHAQ. A moderate positive correlation was found between FACIT-F and EQ-5D (τ =0.625; p < 0.001) and physical functioning (τ = 0.560; p = 0.001) and vitality (τ = 0.777; p < 0.001) domains of SF-36. The remaining SF-36 domains had a weak positive correlation with FACIT-F (Table 1). Regarding mental illness, there was a moderate negative correlation between FACIT-F and HADS-D (τ = -0.638; p < 0.001) and HADS-A (τ =-0.535; p = 0.001).Conclusion:Severe fatigue is frequent among SSc patients. The greater the fatigue, the greater the disability, the lower the quality of life and the worse the score on the scale of depression and anxiety.References:[1]F. Basta, A. Afeltra, D.P.E. Margiotta. Fatigue in systemic sclerosis: a systematic review. Clin Exp Rheumatol 2018; 36 (Suppl. 113): S150-S160[2]Sarah Hewlett, Emma Dures, And Celia Almeida. Measures of Fatigue. Arthritis Care & Research Vol. 63, No. S11, November 2011, pp S263–S286Table 1.Correlation of FACIT-F with measures of disability, quality of life and mental illnessVariablesKendall’s τ coefficientp-valueHAQ-0.6410.000SHAQ - GI involvement-0.3450.039 - Lung involvement-0.4190.011 - Vascular involvement-0.2150.192 - Digital ulcers0.1020.549 - Patient global assessment-0.3250.047EQ-5D0.6250.000SF-36 - Physical functioning0.5600.001 - Role physical0.4910.003 - Bodily pain0.4630.006 - General health0.3410.045 - Vitality0.7770.000 - Social functioning0.4430.009 - Role emotional0.3500.041 - Mental health0.3760.024HADS-D-0.6380.000HADS-A-0.5350.001Disclosure of Interests:None declared

Schistossomiasis is a parasitic disease, caused by helminths of the genus Schistosoma and transmitted in Brazil by snails of the genus Biomphalaria. The municipality of Ouro Preto do Oeste, Rondônia, in the Brazilian Amazon Region, has unusually registered more than 900 cases of schistosomiasis in the last 10 years. The aim of this study was to investigate de potential of transmission of schsitosomiasis in Ouro Preto do Oeste. A total of 1,196 people in a risk area for the disease transmission were requested to answer a clinical-epidemiological survey and to collect feces samples for examination. All the samples that underwent examination resulted negative for S. mansoni. Two hundred and sixty-eight snails were collected in the locality of Ouro Preto do Oeste in 32 different locations. Among these, 44% were classified as belonging to the genus Biomphalaria. Another sample of snails (146 specimens), collected at the same sites, were submitted to an in vitro challenge with Schistosoma mansoni, and none of them were able to transmit the parasite. Finally, we discuss the epidemiological importance of these findings and the lack of attention to a patient with the disease in a non-endemic area. We failed to detected any association between shistossomiasis and the snails from the genus Biomphalaria, that exists in the local, as the planorbids were unable to transmit Shistosoma mansoni. Perhaps the small sample and/or the stool examination technique can have contributed to the results. Further studies, in other localities of Rondônia and with a greater sample could put some light in this question. RESUMO A esquistossomose é uma doença parasitária, causada por helmintos do gênero Schistosoma e transmitida no Brasil por caramujos do gênero Biomphalaria. O município de Ouro Preto do Oeste, Rondônia, Amazônia brasileira, notificou, de forma não usual, mais de 900 casos de esquistossomose mansônica nos últimos 10 anos. O objetivo deste estudo foi investigar o potencial de transmissão da esquistossomose em Ouro Preto do Oeste. Um total de 1.196 pessoas residindo em áreas de risco para a transmissão da doença foram abordadas para responderem um questionário clínico-epidemiológico e realização de exame parasitológico de fezes. Todas as amostras foram negativas para S. mansoni. Duzentos e sessenta e oito caramujos foram coletados em Ouro Preto do Oeste, de 32 localidades diferentes. Entre estes, 44% foram classificados como pertencendo ao gênero Biomphalaria. Outra amostra de caramujos (146 exemplares), coletada nos mesmos locais, foi submetida in vitro a cepas de Schistosoma mansoni, sendo todos incapazes de transmitirem o parasito. Por fim, discute-se a importância epidemiológica desses achados e a falta de atenção ao paciente portador da parasitose em áreas indenes. O estudo não conseguiu demonstrar a ocorrência de transmissão na localidade e nem a habilidade dos planorbídeos locais transmitirem Shistosoma mansoni. Talvez o pequeno tamanho da amostra e/ou a técnica de exame de fezes (pouco sensível) possam ter contribuído para este resultado. Estudos futuros, em outras localidades e com uma amostra maior podem colocar um pouco de luz nesta questão.

Human schistosomiasis, caused by trematode worms of the genusSchistosoma, is one of the most significant neglected tropical diseases, affecting more than 200 million individuals worldwide and praziquantel is the only available drug to treat this disease.Artemisia absinthiumL. andTanacetum partheniumL. are species popularly used as anthelmintics. We investigated thein vitroschistosomicidal activity of crude extracts ofA. absinthium(AA) andT. parthenium(TP) and their isolated compounds. AA and TP, at 200 μg/mL, were active, causing 100% mortality of all adult worms. Chromatographic fractionation of AA leads to isolation of artemetin and hydroxypelenolide, while santin, apigenin, and parthenolide were isolated from TP. Artemetin, hydroxypelenolide, santin, and apigenin, at 100 μM, were inactive against adult worms. Parthenolide (12.5 to 100 μM) caused 100% mortality, tegumental alterations, and reduction of motor activity of all adult worms ofS. mansoni, without affecting mammalian cells. Confocal laser scanning microscopy showed tegumental morphological alterations and changes on the numbers of tubercles ofS. mansoniworms. This report provides the first evidence for thein vitroactivity of parthenolide against adult worms ofS. mansoni, opening the route to further schistosomicidal studies with this compound.

In this study, we evaluated the in vitro and in vivo schistosomicidal activities of chalcones against Schistosoma mansoni worms. In vitro assays revealed that chalcones 1 and 3 were the most active compounds, without affecting significantly mammalian cells. Confocal laser scanning microscopy and scanning electron microscopy studies revealed reduction on the numbers of tubercles and morphological alterations in the tegument of S. mansoni worms after in vitro incubation with chalcones 1 and 3. In a mouse model of schistosomiasis, the oral treatment (400 mg/kg) with chalcone 1 or 3 significantly caused a total worm burden reduction in mice. Chalcone 1 showed significant inhibition of the S. mansoni ATP diphosphohydrolase activity, which was corroborated by molecular docking studies. The results suggested that chalcones could be explored as lead compounds with antischistosomal properties.

Schistosomiasis, caused by helminth flatworms of the genus Schistosoma, is one of the most important parasitic diseases in the world, affecting over 200 million people in developing countries. Riparins are natural alkamides found in Aniba riparia (Lauraceae) fruits that possess several pharmacological properties. In this study, we reported the synthesis, characterization and structural analysis of six riparin derivatives (A-F), as well as their schistosomicidal activity against S. mansoni worms together with a biological, pharmacokinetic and toxicological in silico evaluation. Firstly, these compounds were synthesized, purified and characterized by elemental analysis, FT-IR spectroscopy, X-ray diffraction and theoretical calculations to evaluate their stability and conformation. Next, the schistosomicidal activity of the riparins was tested against S. mansoni worms. Bioassays revealed that Riparins E and F were the most active compounds, showing half-maximum inhibitory concentration at low micromolar ranges (IC50 values ~10 μM). Also, confocal laser scanning microscopy studies revealed tegumental damage in parasites after exposition with Riparins B, E and F. Additionally, based on MTT assay, all tested riparins showed no cytotoxic potential toward mammalian cells. Finally, in silico analyses were used to predict the absorption, distribution, metabolism, elimination and toxicity (ADMET) of the compounds. Taken together, the results revealed a promising ADMET profile and suggested that riparins could be starting points for lead optimization programs for natural products with antischistosomal properties.