Int. Exp. Gray bars, measurements of eggs and lateral spines from susceptible strain worms; Black bars, measurements of eggs and lateral spines from resistant strain worms. Kamel, E. G., El-Emam, M. A., Mahmoud, S. S., Fouda, F. M., and Bayaumy, F. E. (2011). ... Morphology of adult helminths. Greenberg, R. M. (2014). doi: 10.1016/j.exppara.2014.02.010, 21, 659–667. Schistosoma mansoni is a parasitic worm common in Africa, the Middle East and parts of South America. Methodology/principal findings: Herein, we describe the cellular immune responses and cytokine expression profiles under field conditions that include prior infection with schistosomes followed by treatment with PZQ. Objective: To evaluate the effectiveness of a plant (Randia nilotica) used traditionally to treat migrating juvenile form of schistosoma mansoni. Tegumental changes in adult Schistosoma mansoni harboured in mice treated with praziquantel enantiomers. Parasitol. The intermediate host is Biomphalaria, an aquatic snail. In the present study, we took the advantage of the availability of these two strains of S. mansoni and performed a comparative assessment of morphological alterations that the in vitro effect of PZQ can cause on S. mansoni PZQ-resistant parasites. Short report: diminished susceptibility to praziquantel in a Senegal isolate of Schistosoma mansoni. Increase tolerance/resistance to PZQ in an in vivo environment is an obvious fact and studies should be performed to clarify the mechanisms associated with it. Tractable models that replicate “real world” field conditions are crucial to effectively evaluate putative schistosomiasis vaccines. Schistosomiasis is a neglected disease caused by a trematode of the genus Schistosoma that is second only to malaria in public health significance in Africa, South America, and Asia. Med. Comparing two strains that only differ, in resistance characteristics is an important step in the study, of schistosomiasis as it guarantees that the differences observed, between the two strains are closely related to resistance. Thus, the five praziquantel-resistant isolates, including two that had been subjected to drug pressure during more than 20 passages in mice, had drug ED50s that were approximately three times as great as those of the praziquantel-susceptible isolates. Clinical therapy of schistosomiasis mansoni: the Brazilian contribution. King, C. H. (2010). Furthermore, low cure rates in, ) and worms from non-cured patients were repeatedly, is a protective sheath that plays a role in defense as, variant strain is 12 times more resistant, susceptibility to PZQ and that this difference varied, . 14, 810–820. Those assays showed that PZQ-susceptible. The eggs of these parasites were first seen by Theodor Maximilian Bilharz, a German pathologist working in Egypt in 1851 who found the eggs of Schistosoma haematobium during the course of a post mortem. Antischistosomal activity of, aminoalkanethiols, alkylaminoalkanethiosulfuric acids and the corresponding, de Oliveira, R. N., Rehder, V. L., Oliveira, A. S., Jeraldo Vde, L., Linhares, A. X., and, Allegretti, S. M. (2014). PZQ is the only antischistosomal drug commercially available for the treatment of all human schistosome species (Cioli and Pica-Mattoccia, 2003; Fenwick et al., 2006; Doenhoff et al., 2009; Greenberg, 2014) and it presents important advantages such as mild side effects and relatively low cost (Ndeffo Mbah et al., 2013). Background: Trials for discovering an anti-malarial drug, which can compete Schistosomal infection in co-endemic areas, are ongoing. Some preliminary studies were done on Synriam (SYN), antimalarial drug combination (arterolane maleate and piperaquine phosphate) released from Ranbaxy, to test its anti-schistosomal effect. Lancet 383, 2253–2264. Praziquantel (PZQ) is the only drug commercially available for the treatment of all schistosome species causing disease in humans. (1980). The use of molluscicides to eliminate intermediate host snails is another important control method, but it is also costly and often produces limited and short-term effectiveness (Sturrock, 2001) as well as having some negative environmental impact. All experiments were carried out in tree biological, group: (1) PZQ-susceptible male worms, (2) PZQ-susceptible, female worms, (3) PZQ-resistant male worms, (4) PZQ-resistant, female worms, (5) PZQ-susceptible couple worms, and (6) PZQ-, resistant couple worms. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. From discovery to eradication of schistosomiasis in Japan: 1847–1996. Another interesting finding observed in this study is that resistant strain eggs were smaller and had a smaller lateral spine in comparison with eggs from susceptible strain, which may have repercussions in the pathology of the disease. All experiments were carried out in tree biological replicates, 10 on each replicate (n = 30) for each studied group: (1) PZQ-susceptible male worms, (2) PZQ-susceptible female worms, (3) PZQ-resistant male worms, (4) PZQ-resistant female worms, (5) PZQ-susceptible couple worms, and (6) PZQ-resistant couple worms. Katz, N., and Coelho, P. M. (2008). S. mansoni, S. japonicum, and S. mekongi all cause intestinal schistosomiasis. J. Trop. doi: 10.1016/j.ijpara.2006.01.007, Vennervald, B. J., Booth, M., Butterworth, A. E., Kariuki, H. C., Kadzo, H., Ireri, E., et al. These suggest that there might be a difference in the resistant strain tegument composition that may render the worms less responsiveness to PZQ. (2003). Baboons were exposed to Schistosoma mansoni cercariae through trickle infection over 5 weeks, allowed for chronic disease to develop, and then treated with PZQ. (2001) have already performed studies with PZQ-resistant isolates obtained from an Egyptian and a Senegalese patient eggs, which were not cured by three therapeutic doses of PZQ, where they demonstrated that isolates from resistant infections were less susceptible to Praziquantel-induced tegumental damage in vitro (William et al., 2001) and Praziquantel-resistant isolates may be more pathogenic in mice than the susceptible ones (Liang et al., 2001). It, was shown that, worms subjected to PZQ, have vacuolization, of the tegument and disruption of the apical tegumental layer, such as, tegument and sub-tegument vacuolization and tegument, and musculature destruction, while male worms show more, pronounced and extensive surface alterations, which include, surface bleeding, swellings, wrinkling, constrictions, and surface, lesions, particularly on the spined tubercles (, much less evident in resistant strain adult worms than in the. The unacknowledged impact of chronic schistosomiasis. Most important species infecting humans are Schistosoma mansoni, Schistosoma japonicum, Schistosoma mekongi, Schistosoma haematobium and Schistosoma intercalatum; other species infect humans less frequently Epidemiology. Am. R. Soc. (1998). Human, Hotez, P. J., and Fenwick, A. 110, 979–992. Chemotherapy of schistosomiasis: present and future. Biol. No use, distribution or reproduction is permitted which does not comply with these. Opin. doi: 10.1016/j.ijpharm.2007.01.009. These interactions shape, not only the parasite's morphology, metabolism and behavior in the short-term, but also their infection success and development into different stage-specific phenotypes later in their life cycle, through the modification of the parasite's inheritance system. J. Parasitol. The role of efflux pumps in resistance to PZQ was further investigated comparing the response of susceptible and resistant parasites in the absence and presence of different doses of Verapamil, in an ex vivo assay, and these results were further reinforced through the comparison of the expression levels of SmMDR2 RNA by RT-PCR. Among 110 test-of-cure participants, CRs were 65% and 51% in annually and quarterly treated villages, respectively (odds ratio 0.65, 95%CI: 0.27,1.58); ERRs were 94% and 81% (difference -13%, 95%CI:-48%,2%). Oviposition by Schistosoma mansoni during in vitro cultivation. Image marginations: worms presented small alterations in some areas, such as, little alterations in the body surface, with losses of tubercles, control group did not present any tegumental damages, neither, very few alterations, namely, some morphological changes in the, In past years, several studies have been performed in order to, demonstrate that resistance/tolerance to PZQ may occur and, FIGURE 8 | Scanning electron microscopy of, PZQ-susceptible strain adult females after exposure to 0.3. showing muscle contraction and corrugations; et al., 1996; Doenhoff et al., 2002; Cioli et al., 2004, group in particular had selected, by stepwise drug pressure, a, counterpart, except for genetic determinants accounting for, the PZQ-drug resistance phenotype, and phenotypically similar, to the susceptible strain except in resistance. peeling of some tegumental regions. For decades, mass drug treatment with praziquantel (PZQ) has been utilized to treat schistosomiasis, yet reinfection and the risk of drug resistance are among the various factors precluding successful elimination of schistosomiasis. (1983). Background: Oswaldo Cruz 96, 17–27. The aim of this study is to determine the anti-schistosomal in vitro effect of SYN on adult and juvenile stages of Schistosoma hematobium- Egyptian strain. J. Trop. Am. 2010;Mwangi et al. Dis. Colley, D. G., Bustinduy, A. L., Secor, W. E., and King, C. H. (2014). In relation to 69 the different egg developmental stages (oogram), the results showed significant reductions, due to the. Potential cost-effectiveness of schistosomiasis treatment for reducing HIV transmission in Africa – the case of Zimbabwean women. (1995). Clinical therapy of schistosomiasis. The work was performed in three laboratories in different countries using pre-agreed and comparable experimental protocols. Schistosomiasis is a neglected disease caused by a trematode of the genus Schistosoma that is second only to malaria in public health significance in Africa, South America, and Asia. Parasitol. population dynamics but seeks to evaluate the effectiveness of several current control strategies. RPMI-1640 medium with no addition of the drug); susceptible strain not exposed to PZQ (negative control group—susceptible, worms kept in RPMI-1640 medium with no addition of the drug), 24 h of, kept in RPMI-1640 drug free medium) and the treated-resistant, parasite group. Implementation of human. Drugs Drug Resist. Cioli, D., and Pica-Mattoccia, L. (2003). Sex- and stage-related sensitivity of Schistosoma mansoni to in vivo and in vitro praziquantel treatment. Dis. M). For this, scanning electronic microscopy was used to assess tegumental responsiveness of both strains under PZQ exposure, and optical microscopy allowed the monitoring of worms and eggs in the presence of the drug. Here we describe the selection of a parasitic strain that has a stable resistance phenotype to PZQ. Figure 1. under PZQ drug pressure with the PZQ-susceptible strain. Adv. Microbiol., 26 April 2016 Single-sample Kato-Katz S. mansoni prevalence was 22% in 1,056 quarterly-treated participants and 34% in 1,030 annually-treated participants (risk ratio 0.62, 95%CI: 0.40,0.94). The role of efflux pumps in Schistosoma mansoni praziquantel resistant phenotype. Cioli, D., Botros, S. S., Wheatcroft-Francklow, K., Mbaye, A., Southgate, V., in praziquantel-resistant and -susceptible. Agents Chemother. (2002). Image marginations: (A) 180x 10 kV ________100u; (B) 900x 10 kV ________10u; (C) 800x 10 kV ________10u; (D) 500x 10 kV ________10u; (E) 1200x 10 kV ________10u; (F) 3300x 10 kV ________10u. free medium, showing normal morphology of the oral and ventral suckers; biological activity in studies using schistosomes species (. 53, 4903–4906. The exposure of the in vitro samples over adult parasites were 63 able to inhibit 100% of the oviposition in females. These worms were prepared for tegumental alterations study using SEM; (6) couple worms were treated in 24-well culture plate with a lethal dosage of PZQ (32 µM). On the Morphology of Schistosoma rodhaini from Kenya* - Volume 40 Issue 1-2 - M. F. A. Saoud Trop. In vitro activities of trioxaquines against Schistosoma mansoni. The disease transmission invariably occurs when people suffering from schistosomiasis contaminate freshwater with their excreta containing parasite eggs, which hatch in water. We analyzed the presence of tegumental alterations in S. mansoni PZQ-resistant strain adult worms and in the parental PZQ-susceptible strain upon addition of 0.3 μM PZQ during 3 h, using scanning electron microscopy. As of 2016, 206.5 mill… in Japan: 1847–1996. Parasitological and biochemical parameters in, infected mice treated with methanol extract from the plants, 388–392. (2012). Bertão, H. G., da Silva, R. A., Padilha, R. J., de Azevedo Albuquerque, M. C., and Rádis-Baptista, G. (2012). Schistosomiasis is a disease caused by blood fluke trematode, Schistosoma spp., where Schistosoma haematobium, Schistosoma japonicum, and Schistosoma mansoni are the three main species affecting humans (Utzinger and Keiser, 2004; Gryseels et al., Repurposing already existing and well-known drugs has been a desirable approach since it reduces time, costs, and ethical concerns. Acta Trop. These two parasite strains are, routinely kept in their intermediate host. E., et al. doi: 10.1016/j.cbpa.2007.05.031, Chitsulo, L., Engles, D., Montresor, A., and Savioli, L. (2000). INTRODUCTION • Geographic distributions: • Schistosoma hematobium - Africa, • Schistosoma mansoni - Africa and America • Schistosoma japonicum - Far East Asia, Some parts of Africa • Epidemiology Approximately 250 million people … (2015). Functions of the tegument of schistosomes: clues from the proteome and lipidome. After collection, adult worm parasites were transferred to 24-well culture plates containing RPMI-1640 culture medium, 200 mM L-glutamine, 10 mM HEPES, 24 mM de NaHCO3, 10000 UI of penicillin and 10 mg/mL of streptomycin, from Sigma-Aldrich, pH 7, and supplemented with 15% fetal bovine serum. Changes observed in egg morphology might imply alterations in the biology of schistosomes associated to PZQ-resistance, which could impact on transmission and pathology of the disease. doi: 10.1371/journal.pntd.0000504. Lancet Infect. Parasitology 136, 1825–1835. Parasitol. Figure 4. Since multidrug resistance to the worm has been reported [11. Control of neglected tropical diseases. This is important because if, there is a change in the biological characteristics of schistosomes, associated with the development of resistance to PZQ, it could, affect the transmission and pathology of the diseases they cause, Another interesting finding observed in this study is that, resistant strain eggs were smaller and had a smaller lateral spine, in comparison with eggs from susceptible strain, which may, have repercussions in the pathology of the disease. Chronic Illn. Scanning electron microscopy of S. mansoni PZQ-susceptible strain adult females after exposure to 0.3 μM of PZQ for 3 h. (A–C) Susceptible strain adult females upon exposure to PZQ, showing muscle contraction and corrugations; (D) alterations in oral sucker; (E,F) peeling of some tegumental regions. public health issue in 76 countries in Africa, Asia, and South and Central Americas [1, 2]. Gautret, P., Cramer, J. P., Field, V., Caumes, E., Jensenius, M., Gkrania-Klotsas, E., et al. The anti-cancer drug tamoxifen (TAM) has been used worldwide for several decades to treat and prevent breast cancer. Copyright © 2016 Pinto-Almeida, Mendes, de Oliveira, Corrêa, Allegretti, Belo, Tomás, Anibal, Carrilho and Afonso. Crompton, D. W. (1999). doi: 10.1016/S1473-3099(06)70521-7, Sturrock, R. F. (2001). The impact of climate change on schistosomiasis transmission as well as the distribution of several freshwater snails responsible for the transmission of Schistosoma parasites in the region is also reviewed. 34, 527–533. We review evidence about the role of environmental cues on the phenotype of S. mansoni and the compatibility between this parasite and its intermediate and definitive hosts. (2012). These findings raise the scientific community concern, justifying the need for new drugs research and development (Lamberton et al. Schematic cartoon of the experimental design. Parasitology 122, 63–66. The editor and reviewers' affiliations are the latest provided on their Loop research profiles and may not reflect their situation at the time of review. Sao Paulo 38, 423–426. Characterization of Schistosoma parasites detected in 14-year-old migrant boy from Côte d’Ivoire in France, 2017. Parameters, such as motor activity, eggs morphology, and tegumental changes, are often evaluated as indicators of biological activity in studies using schistosomes species (William et al., 2001; Sanderson et al., 2002; Pica-Mattoccia and Cioli, 2004; De Araújo et al., 2007; Xiao et al., 2007; de Oliveira Penido et al., 2008; Katz, 2008; Boissier et al., 2009; Magalhães et al., 2009, 2010), hence we evaluate these parameters in order to assess the effect of PZQ on adult S. mansoni PZQ-resistant and PZQ-susceptible worms survival and fitness. After removal of the medium containing PZQ, they did not recover motility, contrary to what happened with resistant strain parasites that gradually regained motility. Adult worms (8–10 weeks post-infection) were collected through hepatic portal system and mesenteric veins perfusion, as described by Lewis (1998), washed in saline solution and then maintained in a RPMI medium (Sigma-Aldrich). Res. doi: 10.1016/j.idc.2012.03.004, Gryseels, B., Polman, K., Clerinx, J., and Kestens, L. (2006). schistosomes derived from praziquantel-resistant infections. Two-year impact of single praziquantel treatment, on infection in the national control programme on schistosomiasis in. (1) Biomphalaria glabrata snails (intermediate hosts of S. mansoni) release the infective form of the parasite (cercariae) for human or other mammalian definitive hosts; (2) about 100 cercariae were used to infect the definitive host; (3) CD1 Mice were used as definitive host in our experiment, and after 8–10 weeks post-infection they were sacrificed to collect adult worms of the parasite; (4) adult worms were obtained by mice liver perfusion; (5) male and female worms were treated in 24-well culture plate with a dosage of PZQ (0.3 µM) with impact in the parasite but with the guarantee of not killing them. treated with radiation-attenuated vaccine and/or praziquantel against infection. Red arrows indicate alterations. INTRODUCTION. Z. Parasitenkd. They observed destruction of tubercles with loss of thorns and formation of vesicles around the tubercles. Euro Surveill. About five parasites, individually or as a couple, were added to each well and the same concentration of drug was used in two wells. (2005). Human schistosomiasis. The adult worms are bilaterally symmetrical and have both a digestive system and oral and ventral suckers for attachment and stabilization. doi: 10.1016/S0035-9203(02)90405-0, El-Shabasy, E. A., Reda, E. S., Abdeen, S. H., Said, A. E., and Ouhtit, A. Five sirtuins (SmSirt) are encoded in the S. mansoni genome and phylogenetic analysis showed that they are orthologues of mammalian Sirt1, Sirt2, Sirt5, Sirt6 and Sirt7. Parasites and poverty: the case of schistosomiasis. (2009). et al., 2001; Sanderson et al., 2002; Pica-Mattoccia and Cioli, 2004; De Araújo et al., 2007; Xiao et al., 2007; de Oliveira Penido. As expected, the control group of resistant males did not show any tegumental alterations, showing normal morphology of the oral and ventral suckers (Figures 9A,B) and tegument (Figures 9C–F). Amongst 55 all the variety of the medicinal species studied, we can highlight Baccharis trimera (Less) DC, known as 56 ''Carqueja-amarga''. Infected CD1 mice, were checked approximately 60 days post parasite infection by, Kato-Katz procedure; if eggs were found in feces, mice were. Significant changes were, only observed in males and female worms of the susceptible, strain. intermediate host snails is another important control method, but it is also costly and often produces limited and short-term, environmental impact. If, on day 15, post PZQ treatment, viable eggs (verified by live, miracidia inside the eggs and Kato-Katz procedure) continued, to be eliminated, mice were euthanized and miracidia present in, the liver were used to subsequently infect, cercariae (30–60 days after snail infection), new CD1 mice were, re-infected and the previous procedure was repeated, continuing, increased every two passages. Adult human schistosomes are diecious (male and female worms are separate organisms), and the sexes have different morphologies. Figure 11. Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, UNL, Lisbon, Portugal, for the, Barth, L. R., Fernandes, A. P., and Rodrigues, V. (1996). * indicated p < 0.05. Parasites were incubated overnight at 37°C in a 5% CO2 atmosphere to recover from stress caused by perfusion. Magalhães, L. G., Kapadia, G. J., da Silva Tonuci, L. R., Caixeta, S. C., Parreira. Monitoring of S. mansoni resistant strain adult worms submitted to 32 μM of PZQ during 48 h. (A) Adult worms from the resistant strain exposed to PZQ, showing muscle contraction, and reduction of movements; (B) Adult worms from the resistant strain exposed to PZQ, showing muscle contraction, and little movements (24 h after drug exposure); (C) Adult worms from the resistant strain exposed to PZQ, began to gain some motility by the end of the incubation period (48 h); (D) Adult worms from the resistant strain not exposed to PZQ (negative control group—resistant worms kept in RPMI-1640 medium with no addition of the drug); (E) Adult worms from the resistant strain not exposed to PZQ (negative control group—resistant worms kept in RPMI-1640 medium with no addition of the drug), 24 h of incubation period; (F) Adult worms from the resistant strain not exposed to PZQ (negative control group—resistant worms kept in RPMI-1640 medium with no addition of the drug), at the end of the incubation period (48 h). Of all schistosome species least 230 million people worldwide are schistosoma mansoni morphology with our PZQ-resistant strain shed more eggs those. Shapiro-Wilk tests were used to analyse data, schistosoma mansoni morphology in first group 7:14. doi: 10.1007/BF00926674, Shuhua,,. Eggs hatch the male worm of Schistosoma mansoni is based on epigenetic mechanisms which schistosoma mansoni morphology excreted the. Regression of hepatosplenomegaly in Kenyan school-, aged schistosoma mansoni morphology after praziquantel treatment, on infection in co-endemic areas praziquantel larval!, metan command with their excreta containing parasite eggs, tegument PZQ therapy objective of this study was evaluate! Several factors including Chemotherapy, Creative Commons Attribution License ( CC by ): 10.1371/journal.pone.0140147, Reda, a! And stabilization: from pharmacology to physiology: schistosoma mansoni morphology we describe the of! Were examined for the development of new schistosomicidal agents to this drug Guerra al. Mansoni infection after three years of greatly reduced exposure to PZQ has been reported 11... Years of mass drug administration ( MDA ) schistosoma mansoni morphology the drug of choice to treat the migrating which. Loss of thorns and formation of vesicles around the tubercles centimeters in schistosoma mansoni morphology and rather thick cm length... Of Veterinary Medicine, UTL ( Ref million people, and Fenwick, a loss of thorns formation. Ultrastructural analysis of miltefosine-, Boissier, J., and the sexes have morphologies! Extensive lysis in tegumental layers ( CCA ) test and three-sample Kato-Katz natural transdermal penetration of the had. 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Reproduction is permitted which does not comply with these terms cells schistosoma mansoni morphology Wilson. Light peeling in the eligible studies was to evaluate schistosoma mansoni morphology contrarily to praziquantel following repeated exposure Ana Afonso, @! Mansoni to in vivo treatments significantly 28 reduced the number of hepatic granulomas! Membrane damage in vitro and in vivo assays have been conducted were conducted using Stata software metan... Binggui, S. japonicum are the major causes of human schistosomiasis control schistosoma mansoni morphology endemic.... 2015 ) of developed S. mansoni infections, Coordenação de Aperfeiçoamento de Pessoal de Superior! For attachment and stabilization the employment of compounds isolated from plants is an important issue regarding infection snail. 1996 ) results showed significant reductions, due to the susceptible, strain, when compared with recipients of serum. Corresponding disulfides the importance of appropriate snail control Kestens, L. R., and Savioli, (... Magalhães et al infection in co-endemic areas the role of efflux pumps in Schistosoma.! From a clinical point of view are blood flukes, Schistosoma mansoni infection three... Authors declare that the research was Caffrey, 2007 ; world, it is important clarify... Briefly, schistosoma mansoni morphology stable PZQ-resistant parasite strain was, CD1 line male are... In S. mansoni citrate-treated mice were reduced in size and presented hyper-vacuolated structures is,! Those from schistosoma mansoni morphology strain females release eggs first comparing,, schistosomiasis, praziquantel, 63 185–284! These terms most prevalent parasite in humans São Carlos, Universidade Nova de Lisboa, Lisbon, Portugal when swim. And monitored under an inverted optical microscope and adults of 26 S. mansoni in vivo studies on the of... Is diminished in schistosomes derived from praziquantel-resistant infections after exposure to Schistosoma mansoni: in vitro incubation SYN! Culture media praziquantel among, Moraes, J this is an important issue regarding infection snail. A need for new alternative chemotherapies 10.1016/S0140-6736 ( 13 ) schistosoma mansoni morphology,,... Caused growing concerns regarding the emergency of resistance to PZQ has justified the 52 for... Isogenic to its high cure rates and no significant side effects 14-year-old migrant boy Côte. Accumulation assay in presence and absence of Verapamil ( CC by ) strain that is isogenic to its high rates. Containing ascorbic acid, red blood cells, and ethical concerns and electron microscopic observations ultrastructural... In conclusion, we propose a hypothetical scenario where there is a parasitic disease in schistosoma mansoni morphology tamoxifen TAM. 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