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Frontiers in Public Health 2024Baseline mapping showed that schistosomiasis was highly/moderately endemic in nine districts in Sierra Leone. Mass drug administration (MDA) with praziquantel started in...
BACKGROUND
Baseline mapping showed that schistosomiasis was highly/moderately endemic in nine districts in Sierra Leone. Mass drug administration (MDA) with praziquantel started in 2009, and after multiple rounds of treatment, an impact assessment was conducted in 2016 followed by a second re-assessment in 2022 using cluster sampling to provide more granular data for refining chiefdom (sub-district) treatment strategies.
METHODS
On average, 20 rural villages were systematically selected per district by probability proportional to population size across the nine districts. Surveys were conducted in schools, and 24 school children aged between 5 and 14 years were randomly selected, with an equal number of boys and girls. One stool sample and one urine sample were collected per child. Two Kato-Katz slides were examined per stool for infection. Hemastix strips were used as a proxy for infection with urine filtration used for egg counts on hematuria-positive samples.
RESULTS
In total, 4,736 stool samples and 4,618 urine samples were examined across 200 schools in 125 chiefdoms. Overall, the prevalence of was 16.3% (95% CI: 15.3-17.4%), while the overall prevalence of was 2.0% (95% CI: 1.6-2.4%) by hematuria. The prevalence of heavy infections for and was 1.5% (95% CI: 1.1-1.9%) and 0.02% (95% CI: 0.0-0.14%), respectively. Among 125 chiefdoms surveyed, the overall schistosomiasis prevalence was <10% in 65 chiefdoms, 10-49.9% in 47 chiefdoms, and ≥ 50% in 13 chiefdoms. There was a mixed relationship between schistosomiasis in school children and WASH access in schools.
CONCLUSION
Sierra Leone has made significant progress in reducing schistosomiasis prevalence across the country after a decade of MDA intervention. However, high prevalence remains in some hotspot chiefdoms. The next steps are for the national program to investigate and address any potential issues such as low coverage or poor knowledge of schistosomiasis risk behaviors and, where appropriate, consider broadening to community-wide treatment in hotspot chiefdoms or communities.
Topics: Humans; Sierra Leone; Child; Female; Male; Adolescent; Child, Preschool; Praziquantel; Feces; Animals; Mass Drug Administration; Prevalence; Anthelmintics; Schistosomiasis; Schistosoma mansoni; Schistosomiasis mansoni; Rural Population; Endemic Diseases; Cluster Analysis; Schistosoma haematobium
PubMed: 38932788
DOI: 10.3389/fpubh.2024.1415486 -
PloS One 2024Schistosomiasis is a neglected tropical disease which imposes a considerable and enduring impact on affected regions, leading to persistent morbidity, hindering child...
Schistosomiasis is a neglected tropical disease which imposes a considerable and enduring impact on affected regions, leading to persistent morbidity, hindering child development, diminishing productivity, and imposing economic burdens. Due to the emergence of drug resistance and limited management options, there is need to develop additional effective inhibitors for schistosomiasis. In view of this, quantitative structure-activity relationship studies, molecular docking, molecular dynamics simulations, drug-likeness and pharmacokinetics predictions were applied to 39 Schistosoma mansoni Thioredoxin Glutathione Reductase (SmTGR) inhibitors. The chosen QSAR model demonstrated robust statistical parameters, including an R2 of 0.798, R2adj of 0.767, Q2cv of 0.681, LOF of 0.930, R2test of 0.776, and cR2p of 0.746, confirming its reliability. The most active derivative (compound 40) was identified as a lead candidate for the development of new potential non-covalent inhibitors through ligand-based design. Subsequently, 12 novel compounds (40a-40l) were designed with enhanced anti-schistosomiasis activity and binding affinity. Molecular docking studies revealed strong and stable interactions, including hydrogen bonding, between the designed compounds and the target receptor. Molecular dynamics simulations over 100 nanoseconds and MM-PBSA free binding energy (ΔGbind) calculations validated the stability of the two best-designed molecules. Furthermore, drug-likeness and pharmacokinetics prediction analyses affirmed the potential of these designed compounds, suggesting their promise as innovative agents for the treatment of schistosomiasis.
Topics: Molecular Docking Simulation; Molecular Dynamics Simulation; Drug Design; Schistosoma mansoni; Ligands; Animals; Schistosomiasis; Quantitative Structure-Activity Relationship; NADH, NADPH Oxidoreductases; Humans; Multienzyme Complexes
PubMed: 38923997
DOI: 10.1371/journal.pone.0302390 -
Frontiers in Cellular and Infection... 2024has been used for decades as an experimental model for the study of human and porcine cysticercosis. Even though, its life cycle, tissue organization, ultrastructure...
has been used for decades as an experimental model for the study of human and porcine cysticercosis. Even though, its life cycle, tissue organization, ultrastructure and immune response elicited in the host, have been extensively described, there are many other biological questions remaining to be addressed. In the present study we revisited the muscle and neural architecture of cysticerci in two of the most frequently used strains (WFU and ORF), using conventional staining and confocal microscopy imaging, aiming to assemble an updated anatomy. Differences between both strains, including polarization processes during development of the young budding larvae, are emphasized. We also performed a search for genes that have been related to peptidergic neural processes in other related flatworms. These findings can help to understand the anatomical and molecular consequences of the scolex presence or absence in both strains.
Topics: Animals; Larva; Cysticercus; Muscles; Taenia; Microscopy, Confocal; Cysticercosis; Swine; Humans; Nervous System
PubMed: 38919702
DOI: 10.3389/fcimb.2024.1415162 -
BMC Infectious Diseases Jun 2024Schistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. The intravascular worms acquire the nutrients necessary for their survival from...
BACKGROUND
Schistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. The intravascular worms acquire the nutrients necessary for their survival from host blood. Since all animals are auxotrophic for riboflavin (vitamin B2), schistosomes too must import it to survive. Riboflavin is an essential component of the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD); these support key functions of dozens of flavoenzymes.
METHODS
Here, using a combination of metabolomics, enzyme kinetics and in silico molecular analysis, we focus on the biochemistry of riboflavin and its metabolites in Schistosoma mansoni (Sm).
RESULTS
We show that when schistosomes are incubated in murine plasma, levels of FAD decrease over time while levels of FMN increase. We show that live schistosomes cleave exogenous FAD to generate FMN and this ability is significantly blocked when expression of the surface nucleotide pyrophosphatase/phosphodiesterase ectoenzyme SmNPP5 is suppressed using RNAi. Recombinant SmNPP5 cleaves FAD with a Km of 178 ± 5.9 µM and Kcat/Km of 324,734 ± 36,347 M.S. The FAD-dependent enzyme IL-4I1 drives the oxidative deamination of phenylalanine to produce phenylpyruvate and HO. Since schistosomes are damaged by HO, we determined if SmNPP5 could impede HO production by blocking IL-4I1 action in vitro. We found that this was not the case; covalently bound FAD on IL-4I1 appears inaccessible to SmNPP5. We also report that live schistosomes can cleave exogenous FMN to generate riboflavin and this ability is significantly impeded when expression of a second surface ectoenzyme (alkaline phosphatase, SmAP) is suppressed. Recombinant SmAP cleaves FMN with a Km of 3.82 ± 0.58 mM and Kcat/Km of 1393 ± 347 M.S.
CONCLUSIONS
The sequential hydrolysis of FAD by tegumental ecto-enzymes SmNPP5 and SmAP can generate free vitamin B2 around the worms from where it can be conveniently imported by the recently described schistosome riboflavin transporter SmaRT. Finally, we identified in silico schistosome homologs of enzymes that are involved in intracellular vitamin B2 metabolism. These are riboflavin kinase (SmRFK) as well as FAD synthase (SmFADS); cDNAs encoding these two enzymes were cloned and sequenced. SmRFK is predicted to convert riboflavin to FMN while SmFADS could further act on FMN to regenerate FAD in order to facilitate robust vitamin B2-dependent metabolism in schistosomes.
Topics: Riboflavin; Flavin Mononucleotide; Animals; Flavin-Adenine Dinucleotide; Schistosoma mansoni; Mice; Humans; Schistosomiasis mansoni
PubMed: 38918706
DOI: 10.1186/s12879-024-09538-z -
Parasite (Paris, France) 2024The plerocercoid larvae of Spirometra mansoni are etiological agents of human and animal sparganosis. Annexins are proteins with important roles in parasites. However,...
The plerocercoid larvae of Spirometra mansoni are etiological agents of human and animal sparganosis. Annexins are proteins with important roles in parasites. However, our knowledge of annexins in S. mansoni is still inadequate. In this study, 18 new members of the Annexin (ANX) family were characterized in S. mansoni. The clustering analysis demonstrated that all the SmANXs were divided into two main classes, consistent with the patterns of conserved motif organization. The 18 SmANXs were detected at all developmental stages (plerocercoid, adult, and egg) and displayed ubiquitous but highly variable expression patterns in all tissues/organs studied. The representative member rSmANX18 was successfully cloned and expressed. The protein was immunolocalized in the tegument and parenchyma of the plerocercoid and in the tegument, parenchyma, uterus and egg shell of adult worms. The recombinant protein can bind phospholipids with high affinity in a Ca-dependent manner, shows high anticoagulant activity and combines with FITC to recognize apoptotic cells. Annexin gene polymorphism and conservative core motif permutation were found in both cestodes and trematodes. SmANXs also revealed high genetic diversity among Platyhelminthes of medical interest. Our findings lay a foundation for further studies on the biological functions of ANXs in S. mansoni as well as other taxa in which ANXs occur.
Topics: Animals; Spirometra; Phylogeny; Annexins; Amino Acid Sequence; Helminth Proteins; Multigene Family; Humans; Female; Genetic Variation; Recombinant Proteins
PubMed: 38912916
DOI: 10.1051/parasite/2024034 -
Neural Development Jun 2024Acoel flatworms have played a relevant role in classical (and current) discussions on the evolutionary origin of bilaterian animals. This is mostly derived from the... (Review)
Review
Acoel flatworms have played a relevant role in classical (and current) discussions on the evolutionary origin of bilaterian animals. This is mostly derived from the apparent simplicity of their body architectures. This tenet has been challenged over the last couple of decades, mostly because detailed studies of their morphology and the introduction of multiple genomic technologies have unveiled a complexity of cell types, tissular arrangements and patterning mechanisms that were hidden below this 'superficial' simplicity. One tissue that has received a particular attention has been the nervous system (NS). The combination of ultrastructural and single cell methodologies has revealed unique cellular diversity and developmental trajectories for most of their neurons and associated sensory systems. Moreover, the great diversity in NS architectures shown by different acoels offers us with a unique group of animals where to study key aspects of neurogenesis and diversification od neural systems over evolutionary time.In this review we revisit some recent developments in the characterization of the acoel nervous system structure and the regulatory mechanisms that contribute to their embryological development. We end up by suggesting some promising avenues to better understand how this tissue is organized in its finest cellular details and how to achieve a deeper knowledge of the functional roles that genes and gene networks play in its construction.
Topics: Animals; Nervous System; Neurogenesis; Platyhelminths; Biological Evolution; Neurons
PubMed: 38907301
DOI: 10.1186/s13064-024-00187-1 -
Parasitology Research Jun 2024Introduced species have a major impact on freshwater ecosystems, particularly on islands. Numerous fish species have been introduced in Corsica (Mediterranean island,...
Introduced species have a major impact on freshwater ecosystems, particularly on islands. Numerous fish species have been introduced in Corsica (Mediterranean island, southern France) as part of planned programs or clandestinely. The introduction of non-native freshwater fish species can have a range of impacts on the recipient ecosystem, including through the co-introduction of its pathogens. A sample of introduced perch Perca fluviatilis Linnaeus, 1758 from the artificial reservoir of Padula was examined following a report of parasites by an angler. The analyses revealed the occurrence of Eustrongylides sp. (Nematoda) and Clinostomum complanatum (Digenea), two zoonotic parasites in P. fluviatilis. Both parasites are reported for the first time in France. Eustrongylides sp. and C. complanatum may have been introduced with their fish intermediate hosts or through their final bird hosts. The occurrence of the two parasites raises concerns from both a veterinary and human health perspective as they can use a wide range of amphibians as intermediate hosts and can be acquired in humans through the consumption of raw or undercooked fish.
Topics: Animals; France; Fish Diseases; Perches; Introduced Species; Trematoda; Zoonoses; Trematode Infections; Islands; Humans
PubMed: 38898308
DOI: 10.1007/s00436-024-08264-4 -
Nature Communications Jun 2024Schistosomiasis is a neglected tropical disease caused by Schistosoma parasites. Schistosoma are obligate parasites of freshwater Biomphalaria and Bulinus snails, thus...
Schistosomiasis is a neglected tropical disease caused by Schistosoma parasites. Schistosoma are obligate parasites of freshwater Biomphalaria and Bulinus snails, thus controlling snail populations is critical to reducing transmission risk. As snails are sensitive to environmental conditions, we expect their distribution is significantly impacted by global change. Here, we used machine learning, remote sensing, and 30 years of snail occurrence records to map the historical and current distribution of forward-transmitting Biomphalaria hosts throughout Brazil. We identified key features influencing the distribution of suitable habitat and determined how Biomphalaria habitat has changed with climate and urbanization over the last three decades. Our models show that climate change has driven broad shifts in snail host range, whereas expansion of urban and peri-urban areas has driven localized increases in habitat suitability. Elucidating change in Biomphalaria distribution-while accounting for non-linearities that are difficult to detect from local case studies-can help inform schistosomiasis control strategies.
Topics: Animals; Brazil; Schistosoma mansoni; Ecosystem; Biomphalaria; Urbanization; Climate Change; Schistosomiasis mansoni; Snails; Humans
PubMed: 38898012
DOI: 10.1038/s41467-024-48335-9 -
Memorias Do Instituto Oswaldo Cruz 2024The impact of Schistosoma mansoni infection over the immune response and the mechanisms involved in pathogenesis are not yet completely understood.
BACKGROUND
The impact of Schistosoma mansoni infection over the immune response and the mechanisms involved in pathogenesis are not yet completely understood.
OBJECTIVES
This study aimed to evaluate the expression of innate immune receptors in three distinct mouse lineages (BALB/c, C57BL/6 and Swiss) during experimental S. mansoni infection with LE strain.
METHODS
The parasite burden, intestinal tissue oogram and presence of hepatic granulomas were evaluated at 7- and 12-weeks post infection (wpi). The mRNA expression for innate Toll-like receptors, Nod-like receptors, their adaptor molecules, and cytokines were determined at 2, 7 and 12 wpi in the hepatic tissue by real-time quantitative polymerase chain reaction (qPCR).
FINDINGS
Swiss mice showed 100% of survival, had lower parasite burden and intestinal eggs, while infected BALB/c and C57BL/6 presented 80% and 90% of survival, respectively, higher parasite burden and intestinal eggs. The three mouse lineages displayed distinct patterns in the expression of innate immune receptors, their adaptor molecules and cytokines, at 2 and 7 wpi.
MAIN CONCLUSIONS
Our results suggest that the pathogenesis of S. mansoni infection is related to a dynamic early activation of innate immunity receptors and cytokines important for the control of developing worms.
Topics: Animals; Schistosomiasis mansoni; Immunity, Innate; Mice, Inbred BALB C; Mice, Inbred C57BL; Cytokines; Mice; Schistosoma mansoni; Disease Models, Animal; Female; Toll-Like Receptors; Real-Time Polymerase Chain Reaction; Parasite Egg Count; Male; RNA, Messenger; Receptors, Immunologic
PubMed: 38896633
DOI: 10.1590/0074-02760240013 -
International Journal of Molecular... May 2024Flatworms are known for their remarkable regenerative ability, one which depends on totipotent cells known as germinative cells in cestodes. Depletion of germinative...
Flatworms are known for their remarkable regenerative ability, one which depends on totipotent cells known as germinative cells in cestodes. Depletion of germinative cells with hydroxyurea (HU) affects the regeneration of the parasite. Here, we studied the reduction and recovery of germinative cells in cysticerci after HU treatment (25 mM and 40 mM of HU for 6 days) through in vitro assays. Viability and morphological changes were evaluated. The recovery of cysticerci's mobility and morphology was evaluated at 3 and 6 days, after 6 days of treatment. The number of proliferative cells was evaluated using EdU. Our results show morphological changes in the size, shape, and number of evaginated cysticerci at the 40 mM dose. The mobility of cysticerci was lower after 6 days of HU treatment at both concentrations. On days 3 and 6 of recovery after 25 mM of HU treatment, a partial recovery of the proliferative cells was observed. Proteomic and Gene Ontology analyses identified modifications in protein groups related to DNA binding, DNA damage, glycolytic enzymes, cytoskeleton, skeletal muscle, and RNA binding.
Topics: Hydroxyurea; Animals; Cell Proliferation; Taenia; Proteomics; Helminth Proteins; Proteome; Cysticercus
PubMed: 38892261
DOI: 10.3390/ijms25116061