RESUMO
Background: The implication of human Schistosoma mansoni (S. mansoni) infection in concomitance with other risk factors such as hepatitis C virus (HCV) and hepatitis B virus (HBV) in the development of hepatocellular carcinoma (HCC) is still under controversy. This work aimed. to evaluate the role of S. mansoni infection in association with hepatitis B virus (HBV), hepatitis C virus (HCV) and other risk factors in the development and/or progress of HCC. Methods: The present study was carried out on 90 HCC patients recruited from Kafr El-Sheikh Liver Disease Research Institute. After obtaining their informed consents, socio-demographic and clinical data were collected and patients were examined for S. mansoni by Kato-Katz and indirect hemagglutination (IHA) techniques. Alpha-fetoprotein (AFP) level was determined. The Child-Pugh scoring system and Barcelona Clinic Liver Cancer (BCLC) staging system were used to evaluate the pathological features of the studied patients. Results: All participants were negative for active S. mansoni by Kato-Katz. Based on IHA, the participants were categorized into two groups: group I: sixty-two patients negative for S. mansoni and group II: twenty-eight schistosomiasis positive. The patients' age ranged between 40->60, HCC was more prevalent in the age range of > 50-60 years in both groups. Males were more than females and rural participants were more than urban patients in both groups. Most of the patients (88.9%) had HCV while 7.8% had HBV. A higher proportion of HCC patients showed concomitant HCV and S. mansoni (92.6%) than the S. mansoni negative group. The frequency of upper gastrointestinal bleeding (GIB) was four-fold higher among HCC patients positive for schistosomiasis compared to negative schistosomiasis cases (64% vs. 16%). Alpha-fetoprotein (AFP) level was higher in group II than that in group I with no significant difference. Statistical analysis showed no difference between the two studied groups regarding Child scores. On the contrary, BCLC class D was significantly higher among HCC positive schistosomiasis cases compared to the negative group. Conclusion: Concomitant S. mansoni with HCV and HBV potentiate HCC progression.
RESUMO
Schistosomiasis causes severe hepatic fibrosis, making it a global health issue. Moringa oleifera seed oil extract, which had antiparasitic, anti-inflammatory and antioxidant effects, was investigated as an alternative treatment. The 50 mice were divided into control, infected, praziquantel-treated, M. oleifera seed oil extract-treated and combined treatment groups. These treatments were examined for their effects on egg granulomas, hepatic enzymes, total protein, albumin, antioxidant enzymes and pro-inflammatory cytokines. M. oleifera seed oil and/or PZQ significantly reduced egg numbers, granuloma size and liver histopathology. M. oleifera seed oil reduced hepatic enzyme activity, increased total protein and albumin, and increased antioxidant enzyme activity while decreasing malondialdehyde. M. oleifera seed oil reduced the levels of pro-inflammatory cytokines. M. oleifera seed oil may treat schistosomiasis instead of PZQ due to its antifibrotic, immunomodulatory and schistosomicidal properties.
Assuntos
Fígado , Moringa oleifera , Extratos Vegetais , Óleos de Plantas , Esquistossomose mansoni , Sementes , Animais , Moringa oleifera/química , Camundongos , Sementes/química , Óleos de Plantas/farmacologia , Óleos de Plantas/uso terapêutico , Esquistossomose mansoni/tratamento farmacológico , Extratos Vegetais/farmacologia , Fígado/parasitologia , Fígado/patologia , Fígado/efeitos dos fármacos , Schistosoma mansoni/efeitos dos fármacos , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Citocinas/metabolismo , Esquistossomicidas/farmacologia , Esquistossomicidas/uso terapêutico , Granuloma/parasitologia , Granuloma/tratamento farmacológico , Feminino , Masculino , Contagem de Ovos de Parasitas , Praziquantel/farmacologia , Praziquantel/uso terapêutico , Antioxidantes/farmacologiaRESUMO
Schistosomiasis, a parasitic disease caused by Schistosoma spp., affects more than 250 million people worldwide. S. mansoni in particular affects the gastrointestinal tract and, through its eggs, induces a Th2 immune response leading to granuloma formation. The relationship between egg load and immune response is poorly understood. We investigated whether the quantity of parasitic eggs influences the immune response in S. mansoni-infected hamsters. The hepatic and intestinal egg load was assessed, and cytokine expression as well as the expression of three major egg-derived proteins were analyzed in monosex- and bisex-infected animals by qRT-PCR. Statistical correlations between egg load or egg-derived factors Ipse/alpha-1, kappa-5, and omega-1, and the immune response were analyzed in liver and colon tissue. Surprisingly, no correlation of the Th1 cytokines with the hepatic egg load was observed, while the Th2 cytokines Il4, Il5, and Il13 showed an inverse correlation in the liver but not in the colon. A longer embryogenesis of the parasitic eggs in the liver could explain this correlation. This conclusion is supported by the lack of any correlation with immune response in the colon, as the intestinal passage of the eggs is limited to a few days.
Assuntos
Citocinas , Fígado , Schistosoma mansoni , Esquistossomose mansoni , Células Th2 , Animais , Schistosoma mansoni/imunologia , Fígado/parasitologia , Fígado/metabolismo , Citocinas/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/metabolismo , Cricetinae , Contagem de Ovos de Parasitas , Feminino , Mesocricetus , Colo/imunologia , Colo/metabolismo , Colo/parasitologia , Masculino , Proteínas de Helminto/metabolismo , Proteínas de Helminto/imunologia , Proteínas do OvoRESUMO
Schistosomiasis, an endemic neglected tropical disease in areas with poor sanitation, causes physical and mental defects in both children and adults. Various strategies, especially drug administration for morbidity control, have been implemented to combat the disease in Ghana and globally. Despite these efforts, schistosomiasis remains prevalent in Ghana, negatively impacting children's academic performance, growth, and overall quality of life. This study aimed to determine the prevalence of schistosomiasis in school children at Esuekyir, a peri-urban community in Ghana. A cross-sectional study using simple random sampling technique to select participants and collect stool and urine samples from 246 school children in Esuekyir was adopted. Microscopy of urine and stool samples was performed involving urine sedimentation and stool formol-ether sedimentation techniques to analyse for parasite eggs. Questionnaires were developed to help detect risk factors that expose these children to the disease. The prevalence of urogenital schistosomiasis in children at Esuekyir was 15.45% while that of intestinal schistosomiasis was 6.957.0%. There was one case of co-infection of urogenital and intestinal schistosomiasis from a 13 year old primary student. Children in primary school had higher risks of infection due to their activities around the water body. There was a significant association between class groups and urogenital schistosomiasis (p-value = 0.042). The presence of schistosomiasis in school children highlights the importance of targeted interventions and public health initiatives in addressing this specific disease condition especially in primary school children. Findings from the research revealed a higher prevalence of urogenital schistosomiasis in the study population as compared to intestinal schistosomiasis.
Assuntos
Fezes , Esquistossomose , Humanos , Criança , Gana/epidemiologia , Prevalência , Estudos Transversais , Masculino , Feminino , Adolescente , Fezes/parasitologia , Esquistossomose/epidemiologia , Instituições Acadêmicas , Fatores de Risco , Animais , Urina/parasitologia , Estudantes/estatística & dados numéricos , Inquéritos e Questionários , Esquistossomose Urinária/epidemiologiaRESUMO
Malaria and schistosomiasis are infectious diseases that cause hematological profiles abnormalities. Malaria and Schistosoma mansoni co-infection causes exacerbation of health consequences and co-morbidities. The aim of this study was to assess the selected hematological profiles among malaria and S. mansoni co-infected patients at Dembiya Selected Health Institutions. An institutional-based comparative cross-sectional study was conducted from March 30 to August 10, 2022. A total of 140 individuals were enrolled in the study using a convenient sampling technique. Wet mount and Kato Katz technique were conducted to detect S. mansoni in Stool sample. Blood films were prepared for the detection of plasmodium. The data was coded and entered into EpiData version 3.1 before being analyzed with SPSS version 25. A P-value of less than 0.05 was considered statistically significant. Mean of WBC, neutrophil, lymphocyte, eosinophil, RBC, hemoglobin, and hematocrit [4.IU/L,2.2 IU/L, 1.4 IU/L, 0.1 IU/L, 3.13 IU/L, 9.5 g/dL, and 28.7%, resepectively] in co-infected were significantly lower than [7.5 IU/L, 4.6 IU/L, 2.1 IU/L, 0.38 IU/L, 4.8 IU/L, 14.6 g/dL, and 43.7%, resepectively] in the healthy control participants. Mean of RBC, hemoglobin, and hematocrit [3.13 IU/L, 9.5 g/dL, 28.7%, resepectively] in co-infected were significantly lower compared to [3.8 IU/L, 11.5 g/dL, 33.9%, resepectively] in the malaria monoinfected participants and [3.7 IU/L,11.5 g/dL, 33.6%, resepectively] in the S. mansoni monoinfected participants. The result of hematological profiles in healthy participants had no significant difference compared to light,moderate and heavy S. mansoni infection intensity in coinfection. The number of S. mansoni eggs per gram of stool had been negatively correlated with hematological profiles of co-infected participants except lymphocyte and monocyte which correlated positively. Hematological profiles status in coinfection were significantly altered compared to malaria monoinfection, S. mansoni monoinfection, and healthy participants.Therefore, hematological tests should be used to monitor and manage coinfection related complications, and to reduce coinfection associated morbidity and mortality.
RESUMO
Background: Reasons for the high prevalence of Kaposi sarcoma-associated herpesvirus (KSHV) in sub-Saharan Africa, and risk factors leading to viral reactivation and shedding, remain largely undefined. Preliminary studies have suggested that schistosome infection, which has been associated with impaired viral control, is associated with KSHV. In this study we sought to determine the relationship between active Schistosoma mansoni or Schistosoma haematobium infection and KSHV shedding. Methods: We quantified KSHV DNA in saliva and cervical swabs from 2 cohorts of women living in northwestern Tanzanian communities endemic for S mansoni or S haematobium by real-time polymerase chain reaction. χ2 and Fisher exact tests were used to determine differences in clinical and demographic factors between those who were and were not shedding KSHV. Results: Among 139 total women, 44.6% were KSHV seropositive. Six percent of those with S mansoni and 17.1% of those with S haematobium were actively shedding KSHV in saliva and none in cervical samples. Women from the S mansoni cohort who were shedding virus reported infertility more frequently (80% vs 19.5%, P = .009). There was no difference in frequency of KSHV salivary shedding between schistosome-infected and -uninfected women. Conclusions: In an area with high KSHV seroprevalence and endemic schistosome infections, we provide the first report with data demonstrating no association between schistosome infection and salivary or cervical herpesvirus shedding. KSHV salivary shedding was associated with infertility, a known effect of another herpesvirus, human herpesvirus 6.
RESUMO
Background: Mass drug administration of praziquantel is expected to reduce Schistosome carriage in treated children in endemic communities. However, the effectiveness of this annual exercise has not been assessed in Ghana. Therefore, this study aimed to detect viable Schistosoma mansoni infection using point-of-care circulating cathodic antigen (POC-CCA) positivity as proxy and associated factors in children previously treated with praziquantel in an endemic municipality in Ghana. Materials and methods: This cross-sectional study was done in the Assin Central municipality in the Central Region of Ghana. School children, less than 16 years of age, treated with 40 mg/kg of praziquantel (treatment period: February-March 2019), provided early morning urine (â¼40 mL) and stool (â¼4 g) samples. Immediately, POC-CCA (ICT International, South Africa) was done, while S. mansoni ova were detected in formalin fixed samples using microscopy later. Additionally, participant's socio-demographic information and factors associated with S, mansoni infection transmission were collected from each child. Results: A total of 520 children participated in the study (males-51.9%, majority age range [9-11 years, 34.4%]). Overall, 244 (46.9%) were positive for urinary CCA with no S. mansoni detected by microscopy. POC-CCA positivity was higher in females (48.4%), children with 2-3 siblings (49.3%), children aged 6-8-year range (55.4%) and residents of Brofoyedur (52%). However, age (x2 = 16.1, p = 0.0003) and town of residence (x2 = 11.7, p = 0.019) associated with CCA positivity. Further, location of water body (x2 = 16.4, p = 0.008), frequency of water contact (x2 = 12.3, p = 0.015) and handling of the Biomphalaria intermediate host (x2 = 5.1, p = 0.024) associated with POC-CCA outcome. Conclusion: About 47% of the school children were positive for CCA, one year after mass praziquantel administration in the Assin Central municipality. Varied factors associated with the post-praziquantel administration POC-CCA positivity. This study should be replicated in other endemic areas to identify groups at risk of parasite persistence or reinfection to inform modification of control and preventive measures.
RESUMO
Biomphalaria spp. snails are freshwater gastropods that responsible for Schistosoma mansoni transmission. Schistosomiasis is a chronic illness that occurred in underdeveloped regions with poor sanitation. The aim of the present study is to evaluate the molluscicidal activity of benzylamine against B. alexandrina snails and it larvicidal effects on the free larval stages of S. mansoni. Results showed that benzylamine has molluscicidal activity against adult B. alexandrina snails after 24 h of exposure with median lethal concentration (LC50) 85.7 mg/L. The present results indicated the exposure of B. alexandrina snails to LC10 or LC25 of benzylamine resulted in significant decreases in the survival, fecundity (eggs/snail/week) and reproductive rates, acetylcholinesterase, albumin, protein, uric acid and creatinine concentrations, levels of Testosterone (T) and 17ß Estradiol (E), while alkaline phosphatase levels were significantly increased in comparison with control ones. The present results showed that the sub lethal concentration LC50 (85.7 mg/L) of benzylamine has miracidial and cercaricidal activities, where the Lethal Time (LT50) for miracidiae was 17.08 min while for cercariae was 30.6 min. Also, results showed that were decreased significantly after exposure to sub lethal concentrations compared with control. The present results showed that the expression level of NADH dehydrogenase subunit 1 (ND1) genes and cytochrome oxidase subunit I (COI) in B. alexandrina snails exposed to LC10 or LC25 concentrations benzylamine were significantly decreased compared to the control groups. Therefore, benzylamine could be used as effective molluscicide to control schistosomiasis.
Assuntos
Biomphalaria , Larva , Schistosoma mansoni , Animais , Biomphalaria/efeitos dos fármacos , Schistosoma mansoni/efeitos dos fármacos , Larva/efeitos dos fármacos , Moluscocidas/farmacologiaRESUMO
In previous studies, the inhibitory effect of chloroquine on NLRP3 inflammasome and heme production was documented. This may be employed as a double-bladed sword in schistosomiasis (anti-inflammatory and parasiticidal). In this study, chloroquine's impact on schistosomiasis mansoni was investigated. The parasitic load (worm/egg counts and reproductive capacity index [RCI]), i-Nos/Arg-1 expression, splenomegaly, hepatic insult and NLRP3-immunohistochemical expression were assessed in infected mice after receiving early and late repeated doses of chloroquine alone or dually with praziquantel. By early treatment, the least RCI was reported in dually treated mice (41.48 ± 28.58) with a significant reduction in worm/egg counts (3.50 ± 1.29/2550 ± 479.58), compared with either drug alone. A marked reduction in the splenic index was achieved by prolonged chloroquine administration (alone: 43.15 ± 5.67, dually: 36.03 ± 5.27), with significantly less fibrosis (15 ± 3.37, 14.25 ± 2.22) than after praziquantel alone (20.5 ± 2.65). Regarding inflammation, despite the praziquantel-induced significant decrease in NLRP3 expression, the inhibitory effect was marked after dual and chloroquine administration (liver: 3.13 ± 1.21/3.45 ± 1.23, spleen: 5.7 ± 1.6/4.63 ± 2.41). i-Nos RNA peaked with early/late chloroquine administration (liver: 68.53 ± 1.8/57.78 ± 7.14, spleen: 63.22 ± 2.06/62.5 ± 3.05). High i-Nos echoed with a parasiticidal and hepatoprotective effect and may indicate macrophage-1 polarisation. On the flip side, the chloroquine-induced low Arg-1 seemed to abate immune tolerance and probably macrophage-2 polarisation. Collectively, chloroquine synergised the praziquantel-schistosomicidal effect and minimised tissue inflammation, splenomegaly and hepatic fibrosis.
Assuntos
Doenças dos Roedores , Esquistossomose mansoni , Animais , Camundongos , Cloroquina/farmacologia , Regulação para Baixo , Reposicionamento de Medicamentos , Inflamação , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Carga Parasitária , Praziquantel/farmacologia , Esquistossomose mansoni/tratamento farmacológico , EsplenomegaliaRESUMO
Malaria and schistosomiasis are infectious diseases that cause coagulation disorders, biochemical abnormalities, and thrombocytopenia. Malaria and Schistosoma mansoni co-infection cause exacerbations of health consequences and co-morbidities.This study aimed to compare the effect of malaria and Schistosoma mansoni co-infection and malaria infection on selected biochemical and coagulation profiles, and platelet count. An institutional-based comparative cross-sectional study was conducted from March 30 to August 10, 2022. A total of 70 individuals were enrolled in the study using a convenient sampling technique. Wet mount and Kato Katz techniques were conducted to detect Schistosoma mansoni in a stool sample. Blood films were prepared for the detection of plasmodium. The data was coded and entered into EpiData version 3.1 before being analyzed with SPSS version 25. An independent t test was used during data analysis. A P-value of less than 0.05 was considered statistically significant. The mean [SD] of alanine aminotransferase, aspartate aminotransferase, creatinine, total bilirubin, and direct bilirubin in the co-infected was higher than in malaria infected participants. However, the mean of total protein and glucose in co-infected was lower than in the malaria infected participants. The mean of prothrombin time, international normalization ratio, and activated partial thromboplastin time in co-infected was significantly higher, while the platelet count was lower compared to malaria infected participants. Biochemical and coagulation profiles, and platelet count status in co-infection were changed compared to malaria infected participants. Therefore, biochemical and coagulation profiles and platelet count tests should be used to monitor and manage co-infection related complications and to reduce co-infection associated morbidity and mortality.
Assuntos
Coinfecção , Malária , Esquistossomose mansoni , Animais , Humanos , Schistosoma mansoni , Etiópia , Contagem de Plaquetas , Coinfecção/epidemiologia , Coinfecção/complicações , Estudos Transversais , Prevalência , Esquistossomose mansoni/complicações , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/diagnóstico , Malária/complicações , Malária/epidemiologia , Bilirrubina , FezesRESUMO
Schistosomiasis is a major neglected disease that imposes a substantial worldwide health burden, affecting approximately 250â million people globally. As praziquantel is the only available drug to treat schistosomiasis, there is a critical need to identify new anthelmintic compounds, particularly from natural sources. To enhance the activity of different natural products, one potential avenue involves its combination with silver nanoparticles (AgNP). Based on this approach, a one-step green method for the inâ situ preparation of dehydrodieugenol (DHDG) by oxidation coupling reaction using silver and natural eugenol is presented. AgNP formation was confirmed by UV-Vis spectroscopy due to the appearance of the surface plasmon resonance (SPR) band at 430â nm which is characteristic of silver nanoparticles. The nanoparticles were spherical with sizes in the range of 40 to 50â nm. Bioassays demonstrated that the silver nanoparticles loaded with DHDG exhibited significant anthelmintic activity against Schistosoma mansoni adult worms without toxicity to mammalian cells and an inâ vivo animal model (Caenorhabditis elegans), contributing to the development of new prototypes based on natural products for the treatment of schistosomiasis.
Assuntos
Anti-Helmínticos , Anti-Infecciosos , Produtos Biológicos , Eugenol/análogos & derivados , Lignanas , Nanopartículas Metálicas , Esquistossomose , Animais , Humanos , Prata/farmacologia , Prata/química , Nanopartículas Metálicas/química , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Esquistossomose/tratamento farmacológico , Anti-Infecciosos/uso terapêutico , Schistosoma mansoni , Produtos Biológicos/uso terapêutico , MamíferosRESUMO
Schistosomiasis is the second most prevailing parasitic disease worldwide. Although praziquantel is considered an effective drug in the treatment against schistosomiasis to some extent, there is an emerging drug resistance that widely recorded. Therefore, there is an urgent need to develop effective and safe anti-schistosomal drugs. In this study, Cornulaca monacantha (C. monacantha), a sub-saharan plant, was extracted using aqueous ethanol and characterized by High-Performance Liquid Chromatography (HPLC). Major constituents of the extract are belonging to flavonoids, tannins and phenolic glycosides. Worms' viability and surface morphology of Schistosoma mansoni (S. mansoni) adult worms treated with the extract were assessed using in vitro viability assay, Scanning Electron Microscopy (SEM), and histological examination. The extract (80-350 µg/ml) reduced viability percentage of worms by 40-60% and caused degeneration of both oral and ventral suckers, tegumental, sub-tegumental and muscular damage. Molecular docking approach was utilized to assess the binding affinities of the extracted compounds with S. mansoni alpha-carbonic anhydrase (SmCA), an essential tegument protein. Pharmacokinetic analysis using SwissADME showed that 7 compounds have high drug similarity. This study confirms the in vitro schistomicidal activity of C. monacantha extract against S. mansoni adult worms and suggests potential SmCA inhibition.
Assuntos
Esquistossomose mansoni , Esquistossomose , Animais , Simulação de Acoplamento Molecular , Schistosoma mansoni , Praziquantel/farmacologia , Microscopia Eletrônica de Varredura , Esquistossomose mansoni/tratamento farmacológicoRESUMO
Preventive chemotherapy with single-dose praziquantel is the WHO-recommended intervention strategy to eliminate schistosomiasis as a public health problem in endemic countries. Surveillance of drugs used in mass drug administration (MDA) programs is recommended to evaluate its effectiveness in reducing transmissions. After a decade-long implementation of a school-based MDA program in Rwanda, we conducted efficacy surveillance of single-dose praziquantel MDA against S. mansoni infection. Two weeks before MDA, stool examinations were performed to screen MDA-eligible school children (n = 4998) for S. mansoni infection using the Kato-Katz technique, and 265 (6.5%) children tested positive for the infection. All children received praziquantel and albendazole as preventive chemotherapy through the MDA campaign. Infected children were enrolled and followed for efficacy monitoring, and stool examination was repeated after three weeks post-MDA (n = 188). Before treatment, 173 (92%) had a light infection, and 15 (8%) had a moderate infection intensity. The primary and secondary outcomes were parasitological cure and egg reduction rates at three weeks post-treatment. The overall cure and egg reduction rates for S. mansoni infection were 97.9% (95% CI = 94.6-99.4) and 97.02%, respectively. Among the 173 children with light infection intensity, 170 (98.3%, 95% CI = 95.0-99.6) were cured, and among the 15 children who had moderate infection intensity, 14 (93.3%) were cured. No significant association between cure rate and pre-treatment infection intensity was observed. We conclude that single-dose praziquantel is efficacious against light-to-moderate S. mansoni infection. Preventive chemotherapy with praziquantel effectively reduces schistosome reservoirs and transmission among school-age children.
RESUMO
Background: Schistosomiasis is endemic in Cameroon and continues to cause serious public health problems, especially among populations in rural areas. This study aimed at determining the prevalence and risk factors of urinary and intestinal schistosomiasis in Manjo. Method: A cross-sectional study was conducted in the city of Manjo in 2020. Stool and urine samples were collected from 400 participants. These stool and urine samples were examined by the Kato Katz, and centrifugation methods respectively. Results: The results obtained showed an overall prevalence of 6.25%, with 5% and 1.25% for S. mansoni and S. haematobium respectively. A significant difference (p < 0.05) was revealed among occupations, age groups, neighborhood, water usage, educational level, knowledge of the disease meanwhile no significant difference was observed between gender and occupation according to prevalence. The most infected ages were] 50-; + [and]20-35] with 13.36% and 11.86% respectively. S. haematobium revealed a low infection intensity while S. mansoni showed moderate infection intensity. The mean parasite load for S. haematobium was 6 ± 3.225 Eggs/10 ml in females and 7 ± 4.243 Eggs/10 ml for males; while the mean parasitic load in S. mansoni was 180 ± 142.441 Epg in females and 146.67 ± 82.286 Epg in males. Conclusion: Manjo can be classified as a low endemic area with a prevalence rate of 6.25% and species observed were S. haematobium and S. mansoni. Also, risk factors where observed including the use of water from the river for domestic purposes. Therefore, the intensification of health education campaigns among the population would delay the development of this disease in the locality.
RESUMO
Malaria and schistosomiasis are two of the neglected tropical diseases that persistently wreak havoc worldwide. Although many antimalarial drugs such as chloroquine are readily available, the emergence of drug resistance necessitates the development of new therapies to combat this disease. Conversely, Praziquantel (PZQ) remains the sole effective drug against schistosomiasis, but its extensive use raises concerns about the potential for drug resistance to develop. In this project, the concept of molecular hybridization was used as a strategy to design the synthesis of new molecular hybrids with potential antimalarial and antischistosomal activity. A total of seventeen molecular hybrids and two PZQ analogues were prepared by coupling 6-alkylpraziquanamines with cinnamic acids and cyclohexane carboxylic acid, respectively. The synthesised compounds were evaluated for their antimalarial and antischistosomal activity; while all of the above compounds were inactive against Plasmodium falciparum (IC50 > 6 µM), many were active against schistosomiasis with four particular compounds exhibiting up to 100% activity against newly transformed schistosomula and adult worms at 50 µM. Compared to PZQ, the reference drug, the activity of which is 91.7% at 1 µM, one particular molecular hybrid, compound 32, which bears a para-isopropyl group on the cinnamic acid moiety, exhibited a notable activity at 10 µM (78.2% activity). This compound has emerged as the front runner candidate that might, after further optimization, hold promise as a potential lead compound in the fight against schistosomiasis.
Assuntos
Antimaláricos , Esquistossomose , Esquistossomicidas , Animais , Praziquantel/farmacologia , Praziquantel/uso terapêutico , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Schistosoma mansoni , Esquistossomicidas/farmacologia , Esquistossomicidas/uso terapêutico , Esquistossomose/tratamento farmacológicoRESUMO
Hierarchically stacked mesoporous zinc-aluminium nanolayered-double-hydroxide intercalated with decavanadate (ZnAl-LDH-V10O28) is constructed using anion-exchange process via microwave-hydrothermal treatment. Physicochemical properties of ZnAl-LDH-V10O28 are characterized in detail. Decavanadate anions are intimately interacted with ZnAl-LDH nanosheets, generating highly ordered architecture of well-dimensioned stacking blocks of brucite-like nanolayers (â¼8 nm). Such hierarchy improves surface-porosity and electrical-impedivity of ZnAl-LDH-V10O28 with declining its zeta-potential (ζav = 8.8 mV). In-vitro treatment of various developmental-stages of Trichinella spiralis and Schistosoma mansoni by ZnAl-LDH-V10O28 is recognized using parasitological and morphological (SEM/TEM) analyses. ZnAl-LDH-V10O28 exterminates muscle-larvae and adult-worms of Trichinella spiralis, and juvenile and adult Schistosoma mansoni, yielding near 100% mortality with rates achieving 5%/h within about 17 h of incubation. This parasiticidal behavior results from the symphony of biological activity gathering decavanadate and LDH-nanosheets. Indeed, ZnAl-LDH-V10O28 nanohybrid sample, as a promissory biocide for killing food-borne/waterborne parasites, becomes a futuristic research hotspot for studying its in-vivo bioactivity and impact-effectiveness on parasite molecular biology.
RESUMO
Background: Earlier studies found characteristic haematological changes in African patients with active schistosomiasis. If consistently present, full blood counts (FBC) may be helpful to diagnose schistosomiasis also in migrants and returning travellers. Methods: A retrospective patient record review was conducted on data from seven European travel clinics, comparing FBC of Schistosoma egg-positive travellers and migrants to reference values. Sub-analyses were performed for children, returned travellers, migrants and different Schistosoma species. Results: Data analysis included 382 subjects (median age 21.0 years [range 2-73]). In returned travellers, decreases in means of haemoglobin particularly in females (ß = -0.82 g/dL, p = 0.005), MCV (ß = -1.6 fL, p = 0.009), basophils, neutrophils, lymphocytes and monocytes (ß = -0.07, p < 0.001; -0.57, p = 0.012; -0.57, p < 0.001 and -0.13 103/µL, p < 0.001, respectively) were observed. As expected, eosinophils were increased (ß = +0.45 103/µL, p < 0.001). In migrants, a similar FBC profile was observed, yet thrombocytes and leukocytes were significantly lower in migrants (ß = -48 103/µL p < 0.001 and ß = -2.35 103/µL, p < 0.001, respectively). Conclusions: Active egg-producing Schistosoma infections are associated with haematological alterations in returned travellers and migrants. However, these differences are discrete and seem to vary among disease stage and Schistosoma species. Therefore, the FBC is unsuitable as a surrogate diagnostic parameter to detect schistosomiasis.
RESUMO
Objective: Our study investigated the prevalence, infection intensity and associated risk factors of intestinal schistosomiasis among secondary school students in Shinyanga Municipal Council, Northern Tanzania. Methods: A quantitative school-based cross-sectional study was conducted from June to August 2022 among 620 secondary students. One stool specimen per participant was collected and screened for Schistosoma mansoni ova by microscopy using the Kato-Katz technique. Ova were counted to estimate infection intensity in all positive stool samples. Participants' socio-demographic characteristics and risk factors for intestinal schistosomiasis were gathered using a structured questionnaire. Data analysis consisted of descriptive statistics, Chi-square test and logistic regression. Results: Overall prevalence of S. mansoni was 1.9%. All infected participants had light infection intensity. Overall prevalence of other intestinal parasites was 2.7%, with Hookworm spp (17.6%) and Entamoeba coli (52.9%) the most observed intestinal helminth and protozoa, respectively. Among assessed factors, being in form II or III, visiting water sources and doing activities in water sources were statistically significantly associated with increased risk of S. mansoni transmission. Conclusions: There is ongoing transmission of intestinal schistosomiasis among secondary students. Hence, the need for extending praziquantel administration in this group, health education provision, and improvement of water supply, sanitation and hygienic practices.
RESUMO
In many parts of the tropics, schistosomiasis is a major parasitic disease second only to malaria as a cause of morbidity and mortality. Diagnostic approaches include microscopic sampling of excreta such as the Kato-Katz method, radiography, and serology. Due to their vital role in many stages of the parasitic life cycle, proteases have been under investigation as targets of immunological or chemotherapeutic anti-Schistosoma agents. Five major classes of protease have been identified on the basis of the peptide hydrolysis mechanism: serine, cysteine, aspartic, threonine, and metalloproteases. Proteases of all five catalytic classes have been identified from S. mansoni through proteomic or genetic analysis. The study aimed to produce polyclonal antibodies (pAbs) against schistosomal cysteine proteases (CP) to be used in the diagnosis of schistosomiasis. This study was conducted on S. mansoni-infected patients from highly endemic areas and from outpatients' clinic and hospitals and other patients infected with other parasites (Fasciola, hookworm, hydatid, and trichostrongyloids). In this study, the produced polyclonal antibodies against S. mansoni cysteine protease antigens were labeled with horseradish peroxidase (HRP) conjugate and used to detect CP antigens in stool and serum samples of S. mansoni-infected patients by sandwich ELISA. The study involved 200 S. mansoni-infected patients (diagnosed by finding characteristic eggs in the collected stool samples), 100 patients infected with other parasites (Fasciola, hookworm, hydatid, and trichostrongyloids), and 100 individuals who served as parasite-free healthy negative control. The prepared pAb succeeded in detecting CP antigens in stool and serum samples of S. mansoni-infected patients by sandwich ELISA with a sensitivity of 98.5% and 98.0% respectively. A positive correlation was observed between S. mansoni egg counts and both stool and serum antigen concentrations. Purified 27.5 kDa CP could be introduced as a suitable candidate antigen for early immunodiagnosis using sandwich ELISA for antigen detection. KEY POINTS: ⢠Detection of cysteine protease antigens can replace parasitological examination. ⢠Sandwich ELISA has a higher sensitivity than microscopic examination of eggs. ⢠Identification of antigens is important for the goal of obtaining diagnostic tools.
Assuntos
Cisteína Proteases , Esquistossomose mansoni , Animais , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/parasitologia , Proteômica , Antígenos de Helmintos , Sensibilidade e Especificidade , Anticorpos Anti-Helmínticos , Schistosoma mansoni , Fezes , Endopeptidases , Peptídeo Hidrolases , Diagnóstico PrecoceRESUMO
Background & Aims: Schistosomiasis is a parasitic infection which affects more than 200 million people globally. Schistosome eggs, but not the adult worms, are mainly responsible for schistosomiasis-specific morbidity in the liver. It is unclear if S. mansoni eggs consume host metabolites, and how this compromises the host parenchyma. Methods: Metabolic reprogramming was analyzed by matrix-assisted laser desorption/ionization mass spectrometry imaging, liquid chromatography with high-resolution mass spectrometry, metabolite quantification, confocal laser scanning microscopy, live cell imaging, quantitative real-time PCR, western blotting, assessment of DNA damage, and immunohistology in hamster models and functional experiments in human cell lines. Major results were validated in human biopsies. Results: The infection with S. mansoni provokes hepatic exhaustion of neutral lipids and glycogen. Furthermore, the distribution of distinct lipid species and the regulation of rate-limiting metabolic enzymes is disrupted in the liver of S. mansoni infected animals. Notably, eggs mobilize, incorporate, and store host lipids, while the associated metabolic reprogramming causes oxidative stress-induced DNA damage in hepatocytes. Administration of reactive oxygen species scavengers ameliorates these deleterious effects. Conclusions: Our findings indicate that S. mansoni eggs completely reprogram lipid and carbohydrate metabolism via soluble factors, which results in oxidative stress-induced cell damage in the host parenchyma. Impact and implications: The authors demonstrate that soluble egg products of the parasite S. mansoni induce hepatocellular reprogramming, causing metabolic exhaustion and a strong redox imbalance. Notably, eggs mobilize, incorporate, and store host lipids, while the metabolic reprogramming causes oxidative stress-induced DNA damage in hepatocytes, independent of the host's immune response. S. mansoni eggs take advantage of the host environment through metabolic reprogramming of hepatocytes and enterocytes. By inducing DNA damage, this neglected tropical disease might promote hepatocellular damage and thus influence international health efforts.