Treatment Of Schistosomiasis Research Articles

Lyotropic liquid crystal and self-emulsifying drug delivery systems nanoparticles as artesunic acid and praziquantel carriers: An innovative approach for formulation of anti-malaria and schistosomicidal drugs

Praziquantel (PZQ) is the drug of choice for treating cestode and trematode infections, and it is currently the only option against schistosomiasis. Artesunic acid (AcART) is effective against several parasites and has emerged as an alternative for schistosomiasis treatment. However, AcART and PZQ have limited bioavailability due to poor water solubility, low permeability, and rapid cell clearance. To address these challenges, this study aimed to develop self-emulsifying drug delivery systems to develop SEDDS and NPs-LLC to overcome the low water solubility affecting AcART and PZQ bioavailability. The study involved validating the HPLC analytical methodology for AcART, SEDDS, and NPs-LLC formulations, and conducting physicochemical characterization and ex-vivo intestinal permeation assays. The composition of formulations was determined by the solubility balance of AcART and PZQ. The drug content ranged between 83 and 90 %. The anionic zeta potential was attributed to Myverol®, and the particle diameter increased slightly after the drug incorporation, while the polydispersity index indicated the relatively narrow particle size distribution. Additionally, the DSC thermogram confirmed that PZQ and AcART are in solution within SEDDS and NPs-LLC. The FTIR analysis suggests that components of SEDDS and NPs-LLC and drugs do not react to form new chemical species. The selection of specific compound formulations was based on achieving the best solubility balance. The nanostructures were stable and exhibited a surface charge favorable to mucosal permeation, with slightly superior performance for SEDDS. The innovative formulations, SEDDS and NPs-LLC, are suitable and effective carriers for AcART and PZQ.

A Recent Advance in the Diagnosis, Treatment, and Vaccine Development for Human Schistosomiasis.

Schistosomiasis, which affects a large number of people worldwide, is among the most overlooked parasitic diseases. The disease is mainly prevalent in sub-Saharan Africa, southeast Asian countries, and South America due to the lack of adequate sanitation. The disease is mainly associated with poor hygiene, sanitation, and contaminated water, so it is also known as a disease of poverty. Three Schistosoma species (S. mansoni, S. japonicum, and S. haematobium) cause significant human infections. Co-infections with Schistosoma and other parasites are widely common. All these parasites may cause intestinal or urogenital schistosomiasis, where the disease may be categorized into the acute, sensitized, and chronic phases. The disease is more prevalent among school children, which may cause anemia and reduce development. Chronic infections frequently cause significant liver, intestinal, and bladder damage. Women exposed to contaminated water while performing normal duties like washing clothes might acquire urogenital schistosomiasis (UGS), which can cause tissue damage and raise the risk of blood-borne disease transmission, including human immunodeficiency virus (HIV) transmission. Praziquantel (PZQ) is the World Health Organization (WHO)-prescribed treatment for individuals who are known to be infected, but it does not prevent further re-infections with larval worms. Vaccine development and new molecular-based diagnosis techniques have promised to be a reliable approach to the diagnosis and prevention of schistosomiasis. The current review emphasizes the recent advancement in the diagnosis of schistosomiasis by molecular techniques and the treatment of schistosomiasis by combined and alternative regimes of drugs. Moreover, this review has also focused on the recent outbreak of schistosomiasis, the development of vaccines, and their clinical trials.

In vivo anti-schistosomal activity of the methanol extracts from Searsia longipes and Lannea schimperi

Schistosomiasis is a disease caused by the flat worms under the genus Schistosoma. The disease is prominent in tropical and sub tropical countries and it is manifested in two forms; the acute and the chronic form. Treatment and control of the schistosomiasis is constrained with various factors including immerging worm resistance and selective efficacy of the current recommended drug of choice. This therefore calls for the search of new approaches to offset the problems. The aim of this study was to investigate the efficacy of the methanolic extract from Searsia longipes and Lannea schimperi against Schistosoma mansoni by using animal model. Swiss albino mice were used for the efficacy testing, whereby, for each extract, 5 groups of mice were used, and each contained 5 mice. Three different doses were administered to three groups, whereas the remaining two groups were used as negative and positive control arms. Efficacies were assessed based on the reduction of the worm eggs in the faeces and organs, body weight gain, loss of liver weight, as well as reduction of worm burden. Both extracts demonstrated significant egg and worm reduction, which was directly proportional to the dose increment. At the highest dose used, Searsia longipes expressed the higher percentage egg reduction (73.33 %), whereas Lannea schimperi demonstrated the higher worm burden reduction (68.53 %). The present study provides strong evidence of the anti-schistosomal activity of the extracts from both S. longipes and L. schimperi. These findings are a significant step forward, suggesting that these plants could be a promising alternative medicine for the treatment of schistosomiasis. However, further investigations are warranted to isolate the compound responsible for this activity and to assess the sub-acute toxicity of the plant extracts. This next phase of research is crucial for advancing our understanding and potential use of these plant extracts.

Therapeutic efficacy of praziquantel loaded-chitosan nanoparticles on juvenile Schistosoma mansoni worms in murine model

Praziquantel (PZQ) is the standard treatment for schistosomiasis; however, it is poorly effective on immature and juvenile worms. The present study aimed to evaluate the therapeutic efficacy of praziquantel loaded-chitosan nanoparticles (PZQ-CSNPs) on the 25 days old juvenile Schistosoma mansoni worms compared to PZQ and chitosan nanoparticles (CSNPs). It was conducted on 60 Swiss albino mice, including 20 control and 40 experimental mice. The control groups included healthy uninfected and infected non-treated mice. The experimental groups included mice infected treated on the 25th day with 400 mg/kg PZQ, 30 mg/kg CSNPs, 100 mg/kg, and 400 mg/kg PZQ-CSNPs. The results revealed that PZQ-CSNPs (100, 400 mg/kg) gave the best results substantiated by a remarkable decrease in worm burden, egg count, granuloma count and size compared to the other treatments. Moreover, it induced severe deformations of worm morphology regarding oral and ventral suckers, tegument, spines distribution, and male gynaecophoric canal. Liver enzymes and oxidative stress markers were significantly decreased while antioxidant activities were increased compared to control and other treated groups. In conclusion, a single dose of PZQ-CSNPs had significant antischistosomal therapeutic effects during the early maturation phase.

Praziquantel resistance in schistosomes: a brief report

Schistosomiasis is a group of both acute and chronic parasitic trematode infections of the genus Schistosoma. Research into schistosomiasis has been minimal, leading to its classification as a neglected tropical disease, yet more than 140 million people are infected with schistosomes globally. There are no treatments available for early-stage infections, schistosomal dermatitis, or Katayama syndrome, other than symptomatic control with steroids and antihistamines, as the maturing organisms seem to be mostly resistant to typical antiparasitics. However, praziquantel (PZQ) has been the drug of choice for schistosomiasis for decades in the latter stages of the disease. Though it is effective against all three clinically relevant species, heavy reliance on PZQ has led to concerns of schistosome resistance, especially in areas that have implemented this drug in mass drug administration (MDA) programs. This article summarizes the available literature concerning the available evidence for and against a warranted concern for PZQ resistance, genomic studies in schistosomes, proposed mechanisms of resistance, and future research in alternative methods of schistosomiasis treatment.

Combined interventions for the testing and treatment of HIV and schistosomiasis among fishermen in Malawi: a three-arm, cluster-randomised trial

Undiagnosed HIV and schistosomiasis are highly prevalent among fishermen in the African Great Lakes region. We aimed to evaluate the efficacy of lakeside interventions integrating services for HIV and male genital schistosomiasis on the prevalence of schistosomiasis, uptake of antiretroviral therapy (ART) for HIV, and voluntary male medical circumcision (VMMC) among fishermen in Malawi. We conducted a three-arm, cluster-randomised trial in 45 lakeshore fishing communities (clusters) in Mangochi, Malawi. Clusters were defined geographically by their home community as the place where fishermen leave their boats (ie, a landing site). Eligible participants were male fishermen (aged ≥18 years) who resided in a cluster. Clusters were randomly allocated (1:1:1) through computer-generated random numbers to either enhanced standard of care (SOC), which offered invitation with information leaflets to a beach clinic offering HIV testing and referral, and presumptive treatment for schistosomiasis with praziquantel; peer education (PE), in which a nominated fisherman was responsible for explaining the study leaflet to promote services to his boat crew; or peer distribution education (PDE), in which the peer educator explained the leaflet and distributed HIV self-test kits to his boat crew. The beach clinic team and fishermen were not masked to intervention allocation; however, investigators were masked until the final analysis. Coprimary composite outcomes were the proportion of participants who had at least one Schistosoma haematobium egg observed on light microscopy from 10 mL of urine filtrate and the proportion who had self-reported initiating ART or scheduling VMMC by day 28. Outcomes were analysed by intention to treat; multiple imputation for missing outcomes was done; random-effect binomial models adjusting for baseline imbalance and clustering were used to compute unadjusted and adjusted risk differences, risk ratios (RRs) and 95% CIs, and intracluster correlation coefficients for each outcome. This trial is registered with ISRCTN, ISRCTN14354324. Between March 1, 2022, and Jan 29, 2023, 45 (65·2%) of 69 clusters assessed for eligibility were enrolled in the trial, with 15 clusters per arm. Of the 6036 fishermen screened at baseline, 5207 (86·3%) were eligible for participation: 1745 (87·6%) of 1991 in the enhanced SOC group, 1687 (81·9%) of 2061 in the PE group, and 1775 (89·5%) of 1984 in the PDE group. Compared with the prevalence of active schistosomiasis in the enhanced SOC group (292 [16·7%] of 1745), 241 (13·6%) of 1775 fishermen in the PDE group (adjusted RR 0·80 [95% CI 0·69-0·94]; p=0·0054) and 263 (15·6%) of 1687 fishermen in the PE group (0·92 [0·79-1·07]; p=0·28) had schistosomiasis at day 28. 230 (13·2%) in the enhanced SOC group, 281 (16·7%) in the PE group, and 215 (12·1%) in the PDE group initiated ART or were scheduled for VMMC. ART initiation or VMMC scheduling was not significantly increased with the PDE intervention (0·88 [0·74-1·05); p=0·15) and was marginally increased with the PE intervention (1·16 [0·99-1·37]; p=0·069) when compared with the enhanced SOC group. No serious adverse events were reported in this trial. We found weak evidence for the use of peer education to increase uptake of ART and VMMC, but strong evidence for the added distribution of HIV self-test kits to promote high engagement with services and reduce the prevalence of active schistosomiasis, suggesting a high potential for scale-up in hard-to-reach communities across Malawi. Wellcome Trust and the UK National Institute for Health Research.

Increasing uptake of integrated schistosomiasis treatment and HIV screening services in fishermen at high risk of comorbidities in Malawi

Increasing uptake of integrated schistosomiasis treatment and HIV screening services in fishermen at high risk of comorbidities in Malawi

Schistosomiasis in the Military-A Narrative Review.

Schistosomiasis is a parasitosis caused by trematodes of the genus Schistosoma. Humans are infected when coming into contact with freshwater containing the parasites' infective stages, which are amplified through freshwater-dwelling snails acting as intermediate hosts. Schistosomiasis has posed significant problems for troops exposed to freshwater in endemic regions ever since the Napoleonic wars. Schistosomiasis has substantial differences in clinical presentation, depending on the type of parasite, intensity of infection and reinfection, clinical form, and disease stage. It can remain undiagnosed for long periods of time, with well-known long-term morbidity and mortality risks. The diagnosis of schistosomiasis depends on its stage and relays on several tests, all with limitations in sensitivity and specificity. The diagnostic gold standard is the detection of eggs in urine, feces, or tissue biopsies, but this can raise problems in patients such as military personnel, in which the worm burden is usually low. Praziquantel is the drug of choice for schistosomiasis. Currently, there is no available commercial vaccine against any Schistosoma parasite. Avoiding freshwater exposure is the best prevention. Herein, we review the clinical presentation, diagnosis, treatment, and prevention of schistosomiasis in the military. This information may decrease the impact of schistosomiasis on this particular professional group.

The "Doorstop Pocket" In Thioredoxin Reductases─An Unexpected Druggable Regulator of the Catalytic Machinery.

Pyridine nucleotide-disulfide oxidoreductases are underexplored as drug targets, and thioredoxin reductases (TrxRs) stand out as compelling pharmacological targets. Selective TrxR inhibition is challenging primarily due to the reliance on covalent inhibition strategies. Recent studies identified a regulatory and druggable pocket in Schistosoma mansoni thioredoxin glutathione reductase (TGR), a TrxR-like enzyme, and an established drug target for schistosomiasis. This site is termed the "doorstop pocket" because compounds that bind there impede the movement of an aromatic side-chain necessary for the entry and exit of NADPH and NADP+ during enzymatic turnover. This discovery spearheaded the development of new TGR inhibitors with efficacies surpassing those of current schistosomiasis treatment. Targeting the "doorstop pocket" is a promising strategy, as the pocket is present in all members of the pyridine nucleotide-disulfide oxidoreductase family, opening new avenues for exploring therapeutic approaches in diseases where the importance of these enzymes is established, including cancer and inflammatory and infectious diseases.

A Mixed-Methods Evaluation of Mainstreaming Mass Drug Administration for Schistosomiasis and Soil-Transmitted Helminthiasis in Four Districts of Nigeria.

In Nigeria, mass drug administration (MDA) for schistosomiasis (SCH) and soil-transmitted helminthiasis (STH) has often been coordinated with other programs that receive greater external funding. As these programs reach stop MDA milestones, SCH and STH programs will likely need to transition implementation, or "mainstream," to domestic support. A mixed-methods study was conducted in four districts before (2021) and after (2022) mainstreaming to evaluate its impact on MDA coverage. Household surveys were done in 30 villages per district pre- and post-mainstreaming. All selected communities were eligible for STH treatment; around a third were eligible for SCH treatment. Mass drug administration was primarily conducted in schools. A total of 5,441 school-aged children were included in pre-mainstreaming and 5,789 were included in post-mainstreaming. Mass drug administration coverage was heterogeneous, but overall, mebendazole coverage declined nonsignificantly from 81% pre-mainstreaming to 76% post-mainstreaming (P = 0.09); praziquantel coverage declined significantly from 73% to 55% (P = 0.008). Coverage was significantly lower among unenrolled children or those reporting poor school attendance in nearly every survey. For the qualitative component, 173 interviews and 74 focus groups were conducted with diverse stakeholders. Respondents were deeply pessimistic about the future of MDA after mainstreaming and strongly supported a gradual transition to full government ownership. Participants formulated recommendations for effective mainstreaming: clear budgetallocation by governments, robust and targeted training, trust building, and comprehensive advocacy. Although participants lacked confidence that SCH and STH programs could be sustained after reductions in external support, initial results indicate that MDA coverage can remain high 1 year into mainstreaming.

Repeated versus single praziquantel dosing regimen in treatment of female genital schistosomiasis: a phase 2 randomised controlled trial showing no difference in efficacy

Repeated versus single praziquantel dosing regimen in treatment of female genital schistosomiasis: a phase 2 randomised controlled trial showing no difference in efficacy

Schistosomicidal effects of histone acetyltransferase inhibitors against Schistosoma japonicum juveniles and adult worms in vitro.

Schistosomiasis is a relatively neglected parasitic disease that afflicts more than 250 million people worldwide, for which the control strategy relies mainly on mass treatment with the only available drug, praziquantel (PZQ). This approach is not sustainable and is a priority for developing novel drug candidates for the treatment and control of schistosomiasis. In our previous study, we found that DW-3-15, a kind of PZQ derivative, could significantly downregulate the expression of the histone acetyltransferase of Schistosoma japonicum (SjHAT). In this study, several commercially available HAT inhibitors, A485, C646 and curcumin were screened in vitro to verify their antischistosomal activities against S. japonicum juveniles and adults. Parasitological studies and scanning electron microscopy were used to study the primary action characteristics of HAT inhibitors in vitro. Quantitative real-time PCR was employed to detect the mRNA level of SjHAT after treatment with different HAT inhibitors. Our results demonstrated that curcumin was the most effective inhibitor against both juveniles and adults of S. japonicum, and its schistosomicidal effects were time- and dose dependent. However, A485 and C646 had limited antischistosomal activity. Scanning electron microscopy demonstrated that in comparison with DW-3-15, curcumin caused similar tegumental changes in male adult worms. Furthermore, both curcumin and DW-3-15 significantly decreased the SjHAT mRNA level, and curcumin dose-dependently reduced the SjHAT expression level in female, male and juvenile worms. Among the three commercially available HATs, curcumin was the most potent against schistosomes. Both curcumin and our patent compound DW-3-15 markedly downregulated the expression of SjHAT, indicating that SjHAT may be a potential therapeutic target for developing novel antischistosomal drug candidates.

EDBD-3,6-Epidioxy-1,10-Bisaboladiene-An Endoperoxide Sesquiterpene Obtained from Drimys brasiliensis (Winteraceae) Exhibited Potent Preclinical Efficacy against Schistosoma mansoni Infection.

Schistosomiasis, a neglected tropical disease impacting over 250 million individuals globally, remains a major public health challenge due to its prevalence and significant impact on affected communities. Praziquantel, the sole available treatment, highlights the urgency of the need for novel anthelmintic agents to achieve the World Health Organization (WHO) goal of schistosomiasis elimination. Previous studies reported the promising antiparasitic activity of different terpenoids against Schistosoma mansoni Sambon (Diplostomida: Schistosomatidae). In the present work, the hexane extract from branches of Drimys brasiliensis afforded a diastereomeric mixture of endoperoxide sesquiterpenes, including 3,6-epidioxy-bisabola-1,10-diene (EDBD). This compound was evaluated in vitro and in vivo against S. mansoni. EDBD exhibited a significant reduction in S. mansoni viability in vitro, with an effective concentration (EC50) value of 4.1 µM. Additionally, EDBD demonstrated no toxicity to mammalian cells. In silico analysis predicted good drug-likeness properties, adhering to pharmaceutical industry standards, including favorable ADME profiles. Furthermore, oral treatment of S. mansoni-infected mice with EDBD (400 mg/kg) resulted in a remarkable egg burden reduction (98% and 99% in tissues and feces, respectively) surpassing praziquantel's efficacy. These findings suggest the promising potential of EDBD as a lead molecule for developing a novel schistosomiasis treatment.

The synergistic effect of Ficus carica nanoparticles and Praziquantel on mice infected by Schistosoma mansoni cercariae

Bilharzia is a parasitic flatworm that causes schistosomiasis, a neglected tropical illness worldwide. Praziquantel (PZQ) is a commercial single treatment of schistosomiasis so alternative drugs are needed to get rid of its side effects on the liver. The current study aimed to estimate the effective role of Ficus carica nanoparticles (Fc-NPCs), silver nanoparticles (Ag-NPCs) and Ficus carica nanoparticles loaded on silver nanoparticles (Fc-Ag NPCs) on C57BL/6 black female mice infected by Schistosoma mansoni and treated with PZQ treatment. It was proved that schistosomiasis causes liver damage in addition to the PZQ is ineffective as an anti-schistosomiasis; it is recorded in the infected mice group and PZQ treated group as in liver function tests, oxidative stress markers & anti-oxidants, pro-inflammatory markers, pro-apoptotic and anti-apoptotic markers also in liver cells’ DNA damage. The amelioration in all tested parameters has been clarified in nanoparticle-protected mice groups. The Fc-Ag NPCs + PZQ group recorded the best preemptive effects as anti-schistosomiasis. Fc-NPCs, Ag-NPCs and Fc-Ag NPCs could antagonize PZQ effects that were observed in amelioration of all tested parameters. The study showed the phytochemicals’ nanoparticles groups have an ameliorated effect on the health of infected mice.

Evaluation of Therapeutic Efficacy of Mucus and Tissue Extracted from Biomphalaria alexandrina Snails on Mice Infected with Schistosoma mansoni

Abstract Schistosomiasis is a neglected tropical disease with considerable morbidity. Praziquantel though safe and efficacious does not prevent reinfection and the emergence of drug resistance is of great concern. This study was done to evaluate the therapeutic efficacy of mucus and nucleoproteins extracted from Biomphalaria alexandrina snails on miracidia, cercariae and Schistosomamansoni adults in vitro and assess their in vivo effect on mice experimentally infected with Schistosoma mansoni through parasitological, pathological and biochemical parameters.The in vitro study proved that the mucus had a better lethal effect on cercariae than miracidia, on contrast to NPs which was better on miracidia. The mucus effect surpassed the NPs as regard the lethal effect on adults in vitro. The effect of mucus on S. mansoni females and males was almost equivocal except for the effect after 72 hours where 80 µg/ml caused 100% lethal effect on adult females. The effect of NPs on S. mansoni adult females was better than adult males at the highest used concentration of 100 µl/ml after 72 hours with a 60% lethal effect. However, at 48 hours the same concentration had a better lethal impact on males (25%) than females (20%). The in vivostudy proved that the combined NPs or mucus to PZQ added to the effect of individual PZQ considering its effect on ova count, oogram pattern and granuloma parameters. The histopathological results denoted a relevant potential for NPs when compared to the rest of the groups and the control though, the PZQ still showed the best findings. The effect of PZQ alone or combined with mucus or NPs was equivocal resulting in 100% TWB reduction. As regard oxidative stress markers, NO decreased level was best shown by combined PZQ and NPs, while, as regard GSH level, the individual PZQ showed the best increased level. This study concluded that mucus and NPs had cercaricidal, miracidial and antischistosomal effect in vitro and that their combination could be considered as a sharing therapeutic adding to PZQ potentiality in vivo for the treatment of schistosomiasis for further investigations.

Efficacy and safety of single-dose artesunate plus sulfalene/pyrimethamine combined with praziquantel for the treatment of children with Schistosoma mansoni or Schistosoma haematobium in western Kenya: a randomised, open-label controlled trial

BackgroundReliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult and juvenile schistosome worms is urgently needed to improve praziquantel efficacy and delay the potential development of drug resistance. We assessed the efficacy and safety of single-dose praziquantel combined with single-dose artesunate plus sulfalene-pyrimethamine in the treatment of Kenyan children with schistosomiasis.MethodsThis was an open-label, randomised clinical trial involving 426 school-aged children (7–15 years old) diagnosed with Schistosoma mansoni (by Kato-Katz) or S. haematobium (by urine filtration). They were randomly assigned (1:1:1) to receive a single dose of praziquantel (40 mg/kg), a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate) or combination therapy using a single dose of praziquantel (40 mg/kg) combined with a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate). The primary outcome was cure and egg reduction rates at 6 weeks post-treatment in the available case population. Adverse events were assessed within 3 h after treatment.ResultsOf the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data were available for 348 (81.7%) children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and the egg reduction rates were 80.1%, 85.0%, and 88.4% for praziquantel, artesunate plus sulfalene-pyrimethamine, and combination therapy, respectively. For S. haematobium-infected children (n = 145), the corresponding cure rates were 81.4%, 71.1%, and 82.2%, and the egg reduction rates were 95.6%, 97.1%, and 97.7%, respectively. Seventy-one (16.7%) children reported mild-intensity adverse events. The drugs were well tolerated and no serious adverse events were reported.ConclusionsA single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not significantly improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes.Graphical abstract

Unveiling potent inhibitors for schistosomiasis through ligand-based drug design, molecular docking, molecular dynamics simulations and pharmacokinetics predictions.

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.

A qualitative assessment of community perceptions and practices towards schistosomiasis prior to introduction of a potential novel treatment option for preschool-age children in Kenya

BackgroundOver 50 million preschool-age children (PSAC) in Africa need treatment for schistosomiasis but are excluded due to lack of a suitable child-friendly medication. The Paediatric Praziquantel Consortium has developed a novel paediatric formulation for PSAC. In advance of its roll-out, we conducted a social science study to draw lessons to inform implementation.MethodsWe conducted a cross-sectional study in eight villages in two purposively selected highly endemic Kenyan counties (Homa Bay and Kwale). We conducted 17 in-depth interviews with community opinion leaders and 21 with parents/guardians of PSAC. Twelve focus group discussions with parents/guardians of PSAC were also held. The aim was to assess their knowledge, perceptions, practices and willingness to participate in the medication’s roll-out for schistosomiasis. Thematic data analysis was performed.ResultsMost participants had heard of schistosomiasis and perceived it to be a serious disease whose treatment should be prioritised. Others felt it was a common disease that should not cause concern. Some people believed schistosomiasis was caused by witchcraft while others regarded it as a sexually transmitted infection. In addition, some practices like poor human waste disposal and water contact were thought to contribute to continued transmission of the disease.ConclusionCommunity members know and perceive schistosomiasis to be serious, but misinformation about its cause is prevalent. The study suggests the need for increased awareness creation to change the perceptions of communities in relation to schistosomiasis prevention and control. Community sensitisation should be prioritised in advance of medication roll-out.

In vitro and in vivo efficacy of the amiodarone and praziquantel combination against the blood fluke Schistosoma mansoni.

Schistosomiasis, a widespread parasitic disease caused by the blood fluke of the genus Schistosoma, affects over 230 million people, primarily in developing countries. Praziquantel, the sole drug currently approved for schistosomiasis treatment, demonstrates effectiveness against patent infections. A recent study highlighted the antiparasitic properties of amiodarone, an anti-arrhythmic drug, exhibiting higher efficacy than praziquantel against prepatent infections. This study assessed the efficacy of amiodarone and praziquantel, both individually and in combination, against Schistosoma mansoni through comprehensive in vitro and in vivo experiments. In vitro experiments demonstrated synergistic activity (fractional inhibitory concentration index ≤0.5) for combinations of amiodarone with praziquantel. In a murine model of schistosomiasis featuring prepatent infections, treatments involving amiodarone (200 or 400 mg/kg) followed by praziquantel (200 or 400 mg/kg) yielded a substantial reduction in worm burden (60%-70%). Given the low efficacy of praziquantel in prepatent infections, combinations of amiodarone with praziquantel may offer clinical utility in the treatment of schistosomiasis.

Prevalence of intestinal schistosomiasis among school children in Biu Local Government Area, Borno State, Nigeria

Intestinal schistosomiasis is one of the neglected tropical diseases caused by four species of the genus Schistosoma. The aim of this study was to determine the prevalence, knowledge and risk factors associated with intestinal schistosomiasis in the study area. A total number offour hundred and twenty (420) fecal samples were collected from the study participants in the three sampling locations; Tum, Buratai and Biu metropolis. Samples collected were examined using formal-ether concentration technique. Other information about the participants’ knowledge on the disease and associated risk factors were obtained using a structured questionnaire. Three 3(0.7%) out of the entire samples examined were found with the eggs of Schistosoma mansoni and only age group 11-13years and 14-16years 1(0.7%) and 2(1.8%) has egg of Schistosoma mansoni in their fecal samples respectively. All the 3(1.6%) infected participants were male while no female 58 participant was infected with the parasite. Miringa had the highest prevalence of (1.9%) followed by Buratai(0.9%) and no infection in Biu metropolis. The difference in the prevalence rate between the age groups, sexes and locations of th eparticipants was statistically not significant. There was high level of ignorance and poor knowledge about the transmission, prevention and treatment of schistosomiasis among the participants. Other parasites encountered during the study were Ascaris lumbricoides (54%) Trichiuris trichiuria (33%), Giardia intestinalis (3%), Entamoeba histolytica (4%), Ancylostoma duodenale (6%). During this study, Schistosomiasis was not endemic in the study area but other intestinal parasites. Therefore, there is need for stakeholders to educate the people on the effect of this parasite and treat the few infected individuals using praziquantel for schistosoma spp and other anthelmintic drugs for mass administration to avoid further escalation of the intestinal parasites in the area.