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Molecules (Basel, Switzerland) Apr 2024The burden of human schistosomiasis, a known but neglected tropical disease in Sub-Saharan Africa, has been worrisome in recent years. It is becoming increasingly...
The burden of human schistosomiasis, a known but neglected tropical disease in Sub-Saharan Africa, has been worrisome in recent years. It is becoming increasingly difficult to tackle schistosomiasis with praziquantel, a drug known to be effective against all , due to reports of reduced efficacy and resistance. Therefore, this study seeks to investigate the antischistosomal potential of phytochemicals from against proteins that have been implicated as druggable targets for the treatment of schistosomiasis using computational techniques. In this study, sixty-three (63) previously isolated and characterized phytochemicals from were identified from the literature and retrieved from the PubChem database. In silico screening was conducted to assess the inhibitory potential of these phytochemicals against three receptors ( Thioredoxin glutathione reductase, dihydroorotate dehydrogenase, and Arginase) that may serve as therapeutic targets for schistosomiasis treatment. Molecular docking, ADMET prediction, ligand interaction, MMGBSA, and molecular dynamics simulation of the hit compounds were conducted using the Schrodinger molecular drug discovery suite. The results show that Andrographolide possesses a satisfactory pharmacokinetic profile, does not violate the Lipinski rule of five, binds with favourable affinity with the receptors, and interacts with key amino acids at the active site. Importantly, its interaction with dihydroorotate dehydrogenase, an enzyme responsible for the catalysis of the de novo pyrimidine nucleotide biosynthetic pathway rate-limiting step, shows a glide score and MMGBSA of -10.19 and -45.75 Kcal/mol, respectively. In addition, the MD simulation shows its stability at the active site of the receptor. Overall, this study revealed that Andrographolide from could serve as a potential lead compound for the development of an anti-schistosomal drug.
Topics: Azadirachta; Molecular Docking Simulation; Dihydroorotate Dehydrogenase; Animals; Schistosomiasis; Oxidoreductases Acting on CH-CH Group Donors; Humans; Phytochemicals; Molecular Dynamics Simulation; Schistosoma mansoni; NADH, NADPH Oxidoreductases; Plant Extracts; Computer Simulation; Schistosomicides; Multienzyme Complexes; Praziquantel
PubMed: 38731401
DOI: 10.3390/molecules29091909 -
Infectious Diseases of Poverty May 2024Opisthorchiasis and clonorchiasis, caused by Opisthorchis viverrini and Clonorchis sinensis, respectively, are significant yet neglected foodborne trematodiases in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Opisthorchiasis and clonorchiasis, caused by Opisthorchis viverrini and Clonorchis sinensis, respectively, are significant yet neglected foodborne trematodiases in the Great Mekong Subregion (GMS). Despite the reporting of the prevalence of these human liver flukes in the region over the past decades, there has been a lack of a comprehensive and systematic consolidation of this data. Therefore, we aimed to conduct a thorough systematic review and meta-analysis to synthesize and analyze time-trend prevalence estimates of both O. viverrini and C. sinensis across the GMS for the past 30 years.
METHODS
This study undertakes a systematic review using a comprehensive search for published articles in PubMed, EMBASE, Scopus, Cochrane and Thai Journal Online databases until early 2023. The pooled prevalence of O. viverrini and C. sinensis infection was analyzed through a random-effects meta-analysis, with meta-regression analysis used to quantify associations with study characteristics. Sub-group analysis was conducted, whenever comparison data were available, to assess the risk of O. viverrini and C. sinensis infection in each GMS country. Heterogeneity among studies was assessed using the Q statistic and quantified by using the I Index.
RESULTS
From a total of 2997 articles, 155 articles comprising 218 datasets and 751,108 participants were included for review. The GMS prevalence of O. viverrini was 21.11% [45,083/260,237; 95% confidence interval (CI): 17.74-24.47%]. Pooled prevalence estimates were highly observed in Laos (34.06%, 95% CI: 26.85-41.26%), followed by Thailand (18.19%, 95% CI: 13.86-22.51%), and Cambodia (10.48%, 95% CI: 5.52-15.45%). Myanmar and Vietnam had limited data sources for calculation. Clonorchis sinensis infection in GMS was 25.33% (95% CI: 18.32-32.34%), with Guangxi, China, exhibiting the highest prevalence rates at 26.89% (95% CI: 18.34-35.43%), while Vietnam had a prevalence rate of 20.30% (95% CI: 9.13-31.47%). O. viverrini prevalence decreased significantly over time, whereas C. sinensis infection appeared to be stable consistently over time in both China and Vietnam.
CONCLUSIONS
This comprehensive study, drawing from the largest datasets to date, offers an in-depth systematic prevalence review of human liver flukes in the Greater Mekong Subregion. It underscores the imperative for systematic surveillance, data collection, and the implementation of intervention and control measures for these infectious diseases of poverty.
Topics: Animals; Opisthorchiasis; Clonorchiasis; Prevalence; Opisthorchis; Humans; Clonorchis sinensis; Asia, Southeastern
PubMed: 38720371
DOI: 10.1186/s40249-024-01201-8 -
Parasites & Vectors May 2024Schistosomiasis is a neglected tropical disease that afflicts millions of people worldwide; it is caused by Schistosoma, the only dioecious flukes with ZW systems....
BACKGROUND
Schistosomiasis is a neglected tropical disease that afflicts millions of people worldwide; it is caused by Schistosoma, the only dioecious flukes with ZW systems. Schistosoma japonicum is endemic to Asia; the Z chromosome of S. japonicum comprises one-quarter of the entire genome. Detection of positive selection using resequencing data to understand adaptive evolution has been applied to a variety of pathogens, including S. japonicum. However, the contribution of the Z chromosome to evolution and adaptation is often neglected.
METHODS
We obtained 1,077,526 high-quality SNPs on the Z chromosome in 72 S. japonicum using re-sequencing data publicly. To examine the faster Z effect, we compared the sequence divergence of S. japonicum with two closely related species, Schistosoma haematobium and S. mansoni. Genetic diversity was compared between the Z chromosome and autosomes in S. japonicum by calculating the nucleotide diversity (π) and Dxy values. Population structure was also assessed based on PCA and structure analysis. Besides, we employed multiple methods including Tajima's D, F, iHS, XP-EHH, and CMS to detect positive selection signals on the Z chromosome. Further RNAi knockdown experiments were performed to investigate the potential biological functions of the candidate genes.
RESULTS
Our study found that the Z chromosome of S. japonicum showed faster evolution and more pronounced genetic divergence than autosomes, although the effect may be smaller than the variation among genes. Compared with autosomes, the Z chromosome in S. japonicum had a more pronounced genetic divergence of sub-populations. Notably, we identified a set of candidate genes associated with host-parasite co-evolution. In particular, LCAT exhibited significant selection signals within the Taiwan population. Further RNA interference experiments suggested that LCAT is necessary for S. japonicum survival and propagation in the definitive host. In addition, we identified several genes related to the specificity of the intermediate host in the C-M population, including Rab6 and VCP, which are involved in adaptive immune evasion to the host.
CONCLUSIONS
Our study provides valuable insights into the adaptive evolution of the Z chromosome in S. japonicum and further advances our understanding of the co-evolution of this medically important parasite and its hosts.
Topics: Animals; Schistosoma japonicum; Genetic Variation; Host-Parasite Interactions; Evolution, Molecular; Polymorphism, Single Nucleotide; Sex Chromosomes; Selection, Genetic; Schistosoma haematobium; Schistosoma mansoni; Biological Evolution; Schistosomiasis japonica
PubMed: 38720339
DOI: 10.1186/s13071-024-06250-4 -
BMC Veterinary Research May 2024Porcine cysticercosis, a serious zoonotic parasitic disease, is caused by the larvae of Taenia solium and has been acknowledged by the World Organization for Animal...
BACKGROUND
Porcine cysticercosis, a serious zoonotic parasitic disease, is caused by the larvae of Taenia solium and has been acknowledged by the World Organization for Animal Health. The current detection methods of Cysticercus cellulosae cannot meet the needs of large-scale and rapid detection in the field. We hypothesized that the immunofluorescence chromatography test strip (ICS) for detecting Cysticercus cellulosae, according to optimization of a series of reaction systems was conducted, and sensitivity, specificity, and stability testing, and was finally compared with ELISA. This method utilizes Eu-labeled time-resolved fluorescent microspheres (TRFM) coupled with TSOL18 antigen to detect TSOL18 antibodies in infected pig sera.
RESULTS
ICS and autopsy have highly consistent diagnostic results (n = 133), as determined by Cohen's κ analysis (κ = 0.925). And the results showed that the proposed ICS are high sensitivity (0.9459) with specificity (0.9792). The ICS was unable to detect positive samples of other parasites. It can be stored for at least six months at 4℃.
CONCLUSIONS
In summary, we established a TRFM-ICS method with higher sensitivity and specificity than indirect ELISA. Results obtained from serum samples can be read within 10 min, indicating a rapid, user-friendly test suitable for large-scale field detection.
Topics: Animals; Swine; Swine Diseases; Cysticercosis; Sensitivity and Specificity; Antibodies, Helminth; Antigens, Helminth; Fluorescent Antibody Technique; Enzyme-Linked Immunosorbent Assay; Cysticercus; Taenia solium
PubMed: 38720329
DOI: 10.1186/s12917-024-04034-7 -
PLoS Neglected Tropical Diseases May 2024Female genital schistosomiasis (FGS), caused by the parasite Schistosoma haematobium (Sh), is prevalent in Sub-Saharan Africa. FGS is associated with sexual dysfunction...
Female genital schistosomiasis burden and risk factors in two endemic areas in Malawi nested in the Morbidity Operational Research for Bilharziasis Implementation Decisions (MORBID) cross-sectional study.
BACKGROUND
Female genital schistosomiasis (FGS), caused by the parasite Schistosoma haematobium (Sh), is prevalent in Sub-Saharan Africa. FGS is associated with sexual dysfunction and reproductive morbidity, and increased prevalence of HIV and cervical precancerous lesions. Lack of approved guidelines for FGS screening and diagnosis hinder accurate disease burden estimation. This study evaluated FGS burden in two Sh-endemic areas in Southern Malawi by visual and molecular diagnostic methods.
METHODOLOGY/PRINCIPAL FINDINGS
Women aged 15-65, sexually active, not menstruating, or pregnant, were enrolled from the MORBID study. A midwife completed a questionnaire, obtained cervicovaginal swab and lavage, and assessed FGS-associated genital lesions using hand-held colposcopy. 'Visual-FGS' was defined as specific genital lesions. 'Molecular-FGS' was defined as Sh DNA detected by real-time PCR from swabs. Microscopy detected urinary Sh egg-patent infection. In total, 950 women completed the questionnaire (median age 27, [IQR] 20-38). Visual-and molecular-FGS prevalence were 26·9% (260/967) and 8·2% (78/942), respectively. 6·5% of women with available genital and urinary samples (38/584) had egg-patent Sh infection. There was a positive significant association between molecular- and visual-FGS (AOR = 2·9, 95%CI 1·7-5·0). 'Molecular-FGS' was associated with egg-patent Sh infection (AOR = 7·5, 95% CI 3·27-17·2). Some villages had high 'molecular-FGS' prevalence, despite <10% prevalence of urinary Sh among school-age children.
CONCLUSIONS/SIGNIFICANCE
Southern Malawi carries an under-recognized FGS burden. FGS was detectable in villages not eligible for schistosomiasis control strategies, potentially leaving girls and women untreated under current WHO guidelines. Validated field-deployable methods could be considered for new control strategies.
Topics: Humans; Female; Malawi; Adult; Cross-Sectional Studies; Adolescent; Schistosomiasis haematobia; Young Adult; Middle Aged; Risk Factors; Schistosoma haematobium; Animals; Aged; Prevalence; Surveys and Questionnaires; Endemic Diseases
PubMed: 38718065
DOI: 10.1371/journal.pntd.0012102 -
Parasites & Vectors May 2024Opisthorchiasis and cholangiocarcinoma (CCA) continue to be public health concerns in many Southeast Asian countries. Although the prevalence of opisthorchiasis is...
BACKGROUND
Opisthorchiasis and cholangiocarcinoma (CCA) continue to be public health concerns in many Southeast Asian countries. Although the prevalence of opisthorchiasis is declining, reported cases tend to have a light-intensity infection. Therefore, early detection by using sensitive methods is necessary. Several sensitive methods have been developed to detect opisthorchiasis. The immunological detection of antigenic proteins has been proposed as a sensitive method for examining opisthorchiasis.
METHODS
The Opisthorchis viverrini antigenic proteins, including cathepsin B (OvCB), asparaginyl endopeptidase (OvAEP), and cathepsin F (OvCF), were used to construct multi-antigenic proteins. The protein sequences of OvCB, OvAEP, and OvCF, with a high probability of B cell epitopes, were selected using BepiPred 1.0 and the IEDB Analysis Resource. These protein fragments were combined to form OvCB_OvAEP_OvCF recombinant DNA, which was then used to produce a recombinant protein in Escherichia coli strain BL21(DE3). The potency of the recombinant protein as a diagnostic target for opisthorchiasis was assessed using immunoblotting and compared with that of the gold standard method, the modified formalin-ether concentration technique.
RESULTS
The recombinant OvCB_OvAEP_OvCF protein showed strong reactivity with total immunoglobulin G (IgG) antibodies against light-intensity O. viverrini infections in the endemic areas. Consequently, a high sensitivity (100%) for diagnosing opisthorchiasis was reported. However, cross-reactivity with sera from other helminth and protozoan infections (including taeniasis, strongyloidiasis, giardiasis, E. coli infection, enterobiasis, and mixed infection of Echinostome spp. and Taenia spp.) and no reactivity with sera from patients with non-parasitic infections led to a reduced specificity of 78.4%. In addition, the false negative rate (FNR), false positive rate (FPR), positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were 0%, 21.6%, 81.4%, 100%, and 88.9%, respectively.
CONCLUSIONS
The high sensitivity of the recombinant OvCB_OvAEP_OvCF protein in detecting opisthorchiasis demonstrates its potential as an opisthorchiasis screening target. Nonetheless, research on reducing cross-reactivity should be undertaken by detecting other antibodies in other sample types, such as saliva, urine, and feces.
Topics: Opisthorchiasis; Opisthorchis; Animals; Antigens, Helminth; Humans; Antibodies, Helminth; Recombinant Proteins; Sensitivity and Specificity; Helminth Proteins; Epitopes; Cathepsin B; Escherichia coli; Cysteine Endopeptidases
PubMed: 38715089
DOI: 10.1186/s13071-024-06285-7 -
Scientific Reports May 2024Cholangiocarcinoma (CCA) exhibits a heightened incidence in regions with a high prevalence of Opisthorchis viverrini infection, with previous studies suggesting an...
Cholangiocarcinoma (CCA) exhibits a heightened incidence in regions with a high prevalence of Opisthorchis viverrini infection, with previous studies suggesting an association with diabetes mellitus (DM). Our study aimed to investigate the spatial distribution of CCA in relation to O. viverrini infection and DM within high-risk populations in Northeast Thailand. Participants from 20 provinces underwent CCA screening through the Cholangiocarcinoma Screening and Care Program between 2013 and 2019. Health questionnaires collected data on O. viverrini infection and DM, while ultrasonography confirmed CCA diagnoses through histopathology. Multiple zero-inflated Poisson regression, accounting for covariates like age and gender, assessed associations of O. viverrini infection and DM with CCA. Bayesian spatial analysis methods explored spatial relationships. Among 263,588 participants, O. viverrini infection, DM, and CCA prevalence were 32.37%, 8.22%, and 0.36%, respectively. The raw standardized morbidity ratios for CCA was notably elevated in the Northeast's lower and upper regions. Coexistence of O. viverrini infection and DM correlated with CCA, particularly in males and those aged over 60 years, with a distribution along the Chi, Mun, and Songkhram Rivers. Our findings emphasize the association of the spatial distribution of O. viverrini infection and DM with high-risk CCA areas in Northeast Thailand. Thus, prioritizing CCA screening in regions with elevated O. viverrini infection and DM prevalence is recommended.
Topics: Humans; Cholangiocarcinoma; Thailand; Male; Opisthorchiasis; Female; Middle Aged; Opisthorchis; Animals; Bile Duct Neoplasms; Aged; Prevalence; Adult; Spatial Analysis; Diabetes Mellitus; Bayes Theorem; Risk Factors
PubMed: 38714779
DOI: 10.1038/s41598-024-61282-1 -
Proceedings of the National Academy of... May 2024Successful regeneration of missing tissues requires seamless integration of positional information along the body axes. Planarians, which regenerate from almost any...
Successful regeneration of missing tissues requires seamless integration of positional information along the body axes. Planarians, which regenerate from almost any injury, use conserved, developmentally important signaling pathways to pattern the body axes. However, the molecular mechanisms which facilitate cross talk between these signaling pathways to integrate positional information remain poorly understood. Here, we report a () which functionally integrates the anterior-posterior (AP) and the medio-lateral (ML) axes. inhibits WNT/β-catenin signaling along the AP axis and, functions synergistically with the β-catenin-independent WNT signaling of the ML axis. Furthermore, this functional integration is dependent on and -the components of the Hippo/Yorkie (YKI) pathway. Hippo/YKI pathway is a critical regulator of body size in flies and mice, but our data suggest the pathway regulates body axes patterning in planarians. Our study provides a signaling network integrating positional information which can mediate coordinated growth and patterning during planarian regeneration.
Topics: Animals; Body Patterning; Nuclear Proteins; p21-Activated Kinases; Planarians; Protein Serine-Threonine Kinases; Regeneration; Trans-Activators; Wnt Signaling Pathway
PubMed: 38713625
DOI: 10.1073/pnas.2321919121 -
Genome Biology and Evolution May 2024In animals, three main RNA interference mechanisms have been described so far, which respectively maturate three types of small noncoding RNAs (sncRNAs): miRNAs, piRNAs,...
In animals, three main RNA interference mechanisms have been described so far, which respectively maturate three types of small noncoding RNAs (sncRNAs): miRNAs, piRNAs, and endo-siRNAs. The diversification of these mechanisms is deeply linked with the evolution of the Argonaute gene superfamily since each type of sncRNA is typically loaded by a specific Argonaute homolog. Moreover, other protein families play pivotal roles in the maturation of sncRNAs, like the DICER ribonuclease family, whose DICER1 and DICER2 paralogs maturate respectively miRNAs and endo-siRNAs. Within Metazoa, the distribution of these families has been only studied in major groups, and there are very few data for clades like Lophotrochozoa. Thus, we here inferred the evolutionary history of the animal Argonaute and DICER families including 43 lophotrochozoan species. Phylogenetic analyses along with newly sequenced sncRNA libraries suggested that in all Trochozoa, the proteins related to the endo-siRNA pathway have been lost, a part of them in some phyla (i.e. Nemertea, Bryozoa, Entoprocta), while all of them in all the others. On the contrary, early diverging phyla, Platyhelminthes and Syndermata, showed a complete endo-siRNA pathway. On the other hand, miRNAs were revealed the most conserved and ubiquitous mechanism of the metazoan RNA interference machinery, confirming their pivotal role in animal cell regulation.
Topics: Animals; Evolution, Molecular; Phylogeny; RNA Interference; Ribonuclease III; MicroRNAs; RNA, Small Interfering; Argonaute Proteins; Invertebrates
PubMed: 38713108
DOI: 10.1093/gbe/evae098 -
Parasites & Vectors May 2024The role of pathogen genotype in determining disease severity and immunopathology has been studied intensively in microbial pathogens including bacteria, fungi, protozoa...
BACKGROUND
The role of pathogen genotype in determining disease severity and immunopathology has been studied intensively in microbial pathogens including bacteria, fungi, protozoa and viruses but is poorly understood in parasitic helminths. The medically important blood fluke Schistosoma mansoni is an excellent model system to study the impact of helminth genetic variation on immunopathology. Our laboratory has demonstrated that laboratory schistosome populations differ in sporocyst growth and cercarial production in the intermediate snail host and worm establishment and fecundity in the vertebrate host. Here, we (i) investigate the hypothesis that schistosome genotype plays a significant role in immunopathology and related parasite life history traits in the vertebrate mouse host and (ii) quantify the relative impact of parasite and host genetics on infection outcomes.
METHODS
We infected BALB/c and C57BL/6 mice with four different laboratory schistosome populations from Africa and the Americas. We quantified disease progression in the vertebrate host by measuring body weight and complete blood count (CBC) with differential over a 12-week infection period. On sacrifice, we assessed parasitological (egg and worm counts, fecundity), immunopathological (organ measurements and histopathology) and immunological (CBC with differential and cytokine profiles) characteristics to determine the impact of parasite and host genetics.
RESULTS
We found significant variation between parasite populations in worm numbers, fecundity, liver and intestine egg counts, liver and spleen weight, and fibrotic area but not in granuloma size. Variation in organ weight was explained by egg burden and intrinsic parasite factors independent of egg burden. We found significant variation between infected mouse lines in cytokine levels (IFN-γ, TNF-α), eosinophils, lymphocytes and monocyte counts.
CONCLUSIONS
This study showed that both parasite and host genotype impact the outcome of infection. While host genotype explains most of the variation in immunological traits, parasite genotype explains most of the variation in parasitological traits, and both host and parasite genotypes impact immunopathology outcomes.
Topics: Animals; Schistosoma mansoni; Mice; Genotype; Mice, Inbred C57BL; Schistosomiasis mansoni; Mice, Inbred BALB C; Female; Host-Parasite Interactions; Cytokines
PubMed: 38711063
DOI: 10.1186/s13071-024-06286-6