RESUMEN
Schistosomiasis, also known as bilharzia or snail fever, is a tropical parasitic disease resulting from flatworms of the Schistosoma genus. This often overlooked disease has significant impacts in affected regions, causing enduring morbidity, hindering child development, reducing productivity, and creating economic burdens. Praziquantel (PZQ) is currently the only treatment option for schistosomiasis. Given the potential rise of drug resistance and the limited treatment choices available, there is a need to develop more effective inhibitors for this neglected tropical disease (NTD). In view of this, quantitative structure-activity relationship studies (QSAR), molecular docking, molecular dynamics simulations, drug-likeness, and ADMET predictions were applied to 31 inhibitors of Schistosoma mansoni Dihydroorotate dehydrogenase (SmDHODH). The designed QSAR model demonstrated robust statistical parameters including an R2 of 0.911, R2adj of 0.890, Q2cv of 0.686, R2pred of 0.807, and cR2p of 0.825, confirming its robustness. Compound 26, identified as the most active derivative, emerged as a lead candidate for new potential inhibitors through ligand-based drug design. Subsequently, 12 novel compounds (26A-26L) were designed with enhanced inhibition activity and binding affinity. Molecular docking studies revealed strong and stable interactions, including hydrogen bonding and hydrophobic interactions, 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 (26A and 26L). Furthermore, drug-likeness and ADMET prediction analyses affirmed the potential of these designed compounds, suggesting their promise as innovative agents for treating schistosomiasis.
Asunto(s)
Dihidroorotato Deshidrogenasa , Diseño de Fármacos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Relación Estructura-Actividad Cuantitativa , Schistosoma mansoni , Schistosoma mansoni/efectos de los fármacos , Schistosoma mansoni/enzimología , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/antagonistas & inhibidores , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/química , Animales , Esquistosomiasis/tratamiento farmacológico , Ligandos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Humanos , Antihelmínticos/farmacología , Antihelmínticos/química , Descubrimiento de Drogas , Esquistosomiasis mansoni/tratamiento farmacológicoRESUMEN
An experiment was carried out in 1985-87 against schistosomiasis using products neutralizing the intermediate stages of schistosomes. In the laboratory, it had been shown that lauryl betaines, amphoteric substances, used for children's shampoos, quickly immobilized miracidiums and cercariae. Studies in Niger in field conditions with water laden with organic matter gave similar results. This surfactant can be incorporated into ordinary soaps at a dose of 5% without changing their characteristics. Betaine soaps were put on sale in ordinary commercial channels in Niger then in Côte d'Ivoire, in hyperendemic villages for Schistosoma haematobium. Betaines diffused without external intervention into the water used by populations for washing. The soaps were well accepted by these populations. However, after one year, the results in tested villages compared to control ones were unclear on the dynamics of urinary schistosomiasis in terms of prevalence and oviuria. Anti-schistosome treatment seems necessary at the start of the procedure. The use of soap by populations needed to be measured. In conclusion, this promising laboratory action deserves to be evaluated again in the field, in addition to health education and systematic treatment actions.
Asunto(s)
Esquistosomiasis , Jabones , Humanos , Esquistosomiasis/prevención & control , Esquistosomiasis/epidemiología , Esquistosomiasis/tratamiento farmacológico , Côte d'Ivoire/epidemiología , Niger/epidemiología , Animales , Esquistosomiasis Urinaria/prevención & control , Esquistosomiasis Urinaria/tratamiento farmacológico , Esquistosomiasis Urinaria/epidemiologíaRESUMEN
BACKGROUND: Acute schistosomiasis occurs most often in travelers to endemic regions. The aim of the study is to describe the epidemiological, clinical and parasitological characteristics of patients with schistosomiasis acquired during an international travel. METHODS: Observational retrospective study including all travel-related schistosomiasis cases seen at the International Health Unit Vall d'Hebron-Drassanes (Barcelona, Spain) from 2009 to 2022. Diagnosis of schistosomiasis was defined by the presence of Schistosoma eggs in stools or urine or the positivity of a serological test. We collected demographic, epidemiological, clinical, parasitological, and therapeutic information. RESULTS: 917 cases of schistosomiasis were diagnosed, from whom 96 (10.5 %) were travel-related. Mean age of the patients was 34.9 years, and 53.1 % were women. Median duration of the travel was 72 days, and geographical areas where travelers had contact with fresh water were Africa (82.3 %), Asia (12.5 %), and South America (5.2 %). Twenty (20.8 %) patients reported having had some clinical symptom, being gastrointestinal symptoms the most frequent. Two patients developed the classical Katayama syndrome. In eleven (11.5 %) cases eggs were observed in urine or feces samples, and 85 (88.5 %) cases were diagnosed by a positive serology. Ninety-one (94.8 %) patients received treatment with praziquantel with different therapeutic schemes. The two patients with Katayama syndrome received concomitant treatment with corticosteroids. CONCLUSIONS: Schistosomiasis in travelers represented 10 % of the overall schistosomiasis cases in our center. Increasing the awareness in the pre-travel advice and implementing specific screening in those travelers at risk (long travelers, contact with fresh water) could reduce the incidence and associated morbidity in this group.
Asunto(s)
Esquistosomiasis , Viaje , Medicina Tropical , Humanos , España/epidemiología , Femenino , Masculino , Estudios Retrospectivos , Adulto , Esquistosomiasis/epidemiología , Esquistosomiasis/diagnóstico , Esquistosomiasis/tratamiento farmacológico , Persona de Mediana Edad , Praziquantel/uso terapéutico , Enfermedades Transmisibles Importadas/epidemiología , Enfermedades Transmisibles Importadas/parasitología , Enfermedades Transmisibles Importadas/diagnóstico , Enfermedades Transmisibles Importadas/tratamiento farmacológico , Heces/parasitología , Animales , Antihelmínticos/uso terapéutico , Adulto Joven , AdolescenteRESUMEN
BACKGROUND: Species hybridization represents a real concern in terms of parasite transmission, epidemiology and morbidity of schistosomiasis. It is greatly important to better understand the impact of species hybridization for the clinical management. METHODS: A prospective observational study was carried out in sub-Saharan migrants who were diagnosed with confirmed genitourinary schistosomiasis. A tailored protocol was applied, including Schistosoma serology, a specific urine LAMP tests for schistosomiasis and an ultrasound examination before treatment with praziquantel. A scheduled follow-up was performed at 3, 6 and 12 months to monitor treatment response, comparing patients carriers of Schistosoma hybrids with carriers of only genetically pure forms. RESULTS: A total of 31 male patients from West Africa were included in the study with a mean age of 26.5 years. Twelve (38.7 %) of the patients were carriers of Schistosoma hybrids. As compared with patients infected with S. haematobium alone, hybrid carriers had lower haemoglobin levels (13.8 g/dL [SD 1.8] vs 14.8 g/dL [SD 1.4], p = 0.04), a greater frequency of hematuria (100 % vs 52.6 %, p = 0.005), a higher ultrasound score (2.64, SD 2.20 vs 0.89, SD 0.99; p = 0.02). However, the presence of hybrids did not result in differences in clinical and analytical responses after treatment. CONCLUSIONS: The presence of Schistosoma hybrids seems to cause increased morbidity in infected individuals. However, it does not appear to result in differences in diagnostic tests or in clinical and analytical responses after treatment.
Asunto(s)
Hibridación Genética , Praziquantel , Humanos , Masculino , Estudios Prospectivos , Adulto , Animales , Praziquantel/uso terapéutico , Esquistosomiasis Urinaria/tratamiento farmacológico , Esquistosomiasis Urinaria/diagnóstico , Esquistosomiasis Urinaria/epidemiología , Adulto Joven , Antihelmínticos/uso terapéutico , Schistosoma haematobium/genética , Schistosoma haematobium/aislamiento & purificación , Schistosoma/genética , Schistosoma/aislamiento & purificación , Adolescente , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis/epidemiología , Esquistosomiasis/diagnóstico , África Occidental/epidemiología , Persona de Mediana Edad , Migrantes/estadística & datos numéricosRESUMEN
Schistosomiasis is the second most important parasitic disease of public health importance in Africa, affecting over 50 million children aged <5 years old. Schistosomiasis control has focused on treating school-aged children (>6 years) and adults through mass drug administration (MDA). Following the recent development of a paediatric praziquantel (PZQ) formulation for children aged <5 years, there are now concerted efforts to determine optimal and effective ways to integrate treatment of these children into national schistosomiasis control programmes. In this opinion article we outline the pathway for successful drug access, delivery, and mainstreaming of the new formulation in endemic country health systems. Effective and sustained paediatric schistosomiasis treatment is an important target of the 2030 World Health Organization (WHO) neglected tropical diseases (NTDs) roadmap.
Asunto(s)
Antihelmínticos , Praziquantel , Esquistosomiasis , Praziquantel/uso terapéutico , Praziquantel/administración & dosificación , Humanos , Esquistosomiasis/tratamiento farmacológico , Preescolar , Antihelmínticos/uso terapéutico , Antihelmínticos/administración & dosificación , Niño , Administración Masiva de Medicamentos , África/epidemiologíaRESUMEN
BACKGROUND: Schistosomiasis is one of the endemic parasitic diseases in many developing countries. Despite this, appendicitis secondary to schistosomiasis is an uncommon condition even in some endemic areas. Schistosomal appendicitis, an incidentally discovered appendicitis associated with schistosomiasis histological findings, affects young males predominantly. Timely diagnosis and treatment, including appendectomy and anti-helminthic therapy, are crucial. CASE REPORT: A 24-year-old Sudanese male patient presented with abdominal pain. Diagnosed with acute appendicitis, he underwent appendectomy, revealing appendix inflammation with Schistosoma ova in histopathology. Abdominal ultrasound detected no complications. Weakly positive Schistosoma serology was noted, but stool and urine analysis showed no infection evidence. Prescribed praziquantel, patient had 3-year post-op follow-up without complications. CONCLUSIONS: This case report underscores the significance of including schistosomiasis in the differential diagnosis of appendicitis, particularly in regions where the disease is endemic. It underscores the necessity of histopathological evaluations for accurate diagnosis, emphasizing the potential implications for clinical practice in similar settings.
Asunto(s)
Antihelmínticos , Apendicectomía , Apendicitis , Praziquantel , Esquistosomiasis , Humanos , Apendicitis/parasitología , Apendicitis/diagnóstico , Masculino , Adulto Joven , Praziquantel/uso terapéutico , Antihelmínticos/uso terapéutico , Esquistosomiasis/diagnóstico , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis/complicaciones , Diagnóstico Diferencial , Dolor Abdominal/etiología , Dolor Abdominal/parasitología , Ultrasonografía , Animales , Resultado del Tratamiento , Apéndice/parasitología , Apéndice/patología , Apéndice/diagnóstico por imagenRESUMEN
Schistosomiasis is a neglected zoonotic parasitic disease. Currently, praziquantel is the drug of choice for the treatment of schistosomiasis, and is the only effective chemical for treatment of schistosomiasis japonica. Since its introduction in the 1970s, praziquantel has been used for large-scale chemotherapy of schistosomiasis for over 40 years. However, there have been reports pertaining to the resistance to praziquantel in schistosomes. Therefore, development of novel antischistosomal agents as alternatives of praziquantel, is of great need. Histone deacetylases and histone acetyltransferases have been recently reported to play critical roles in the growth, development and reproduction of schistosomes, and are considered as potential drug targets for the treatment of schistosomiasis. This review summarizes the latest advances of histone deacetylase and histone acetyltransferase inhibitors in the research on antischistosomal drugs, so as to provide insights into research and development of novelantischistosomal agents.
Asunto(s)
Histona Acetiltransferasas , Inhibidores de Histona Desacetilasas , Histona Desacetilasas , Animales , Inhibidores de Histona Desacetilasas/farmacología , Histona Acetiltransferasas/antagonistas & inhibidores , Humanos , Histona Desacetilasas/metabolismo , Schistosoma/efectos de los fármacos , Schistosoma/enzimología , Schistosoma/fisiología , Esquistosomiasis/tratamiento farmacológico , Esquistosomicidas/farmacología , Esquistosomicidas/uso terapéuticoRESUMEN
BACKGROUND: Schistosomiasis is a debilitating neglected tropical disease endemic in sub-Saharan Africa. The role of health facilities in the prevention, diagnosis, control, and elimination of schistosomiasis is poorly documented. In a setting targeted for schistosomiasis elimination in Zanzibar, we assessed the prevalence of Schistosoma haematobium among patients seeking care in a health facility and investigated schistosomiasis-related knowledge of staff, and health facilities' capacities and needs for schistosomiasis diagnosis and management. METHODS: We conducted a health facility-based mixed-method study on Pemba Island from June to August 2023. Patients aged ≥ 4 years seeking care in four health facilities were screened for S. haematobium infection using urine filtration and reagent strips. Those patients aged ≥ 10 years were additionally interviewed about signs and symptoms. Staff from 23 health facilities responded to a questionnaire assessing knowledge and practices. Ten staff participated in a focus group discussion (FGD) about capacities and needs for schistosomiasis diagnosis and management. RESULTS: The prevalence of S. haematobium infection in patients attending the health facilities, as determined by the presence of eggs in urine, was 1.1% (8/712). Microhaematuria was detected in 13.3% (95/712) of the patients using reagent strips. Among patients responding to the questionnaire, pelvic pain, pain during sex, and painful urination were reported by 38.0% (237/623), 6.3% (39/623), and 3.2% (20/623), respectively. Among the health facility staff, 90.0% (44/49) and 87.8% (43/49) identified blood in urine and pelvic pain, respectively, as symptoms of urogenital schistosomiasis, 81.6% (40/49) and 93.9% (46/49) reported collecting a urine sample and pursuing a reagent strip test, respectively, for diagnosis, and 87.8% (43/49) administered praziquantel for treatment. The most reoccurring themes in the FGD were the need for more staff training about schistosomiasis, requests for diagnostic equipment, and the need to improve community response to schistosomiasis services in health facilities. CONCLUSIONS: The prevalence of S. haematobium infection in patients seeking care in health facilities in Pemba is very low and similar to what has been reported from recent community-based cross-sectional surveys. The health facility staff had good schistosomiasis-related knowledge and practices. However, to integrate schistosomiasis patient management more durably into routine health facility activities, scalable screening pathways need to be identified and capacities need to be improved by regular staff training, and an unbroken supply of accurate point-of-care diagnostics and praziquantel for the treatment of cases.
Asunto(s)
Instituciones de Salud , Schistosoma haematobium , Esquistosomiasis Urinaria , Humanos , Femenino , Masculino , Niño , Prevalencia , Esquistosomiasis Urinaria/diagnóstico , Esquistosomiasis Urinaria/epidemiología , Esquistosomiasis Urinaria/tratamiento farmacológico , Esquistosomiasis Urinaria/prevención & control , Adulto , Schistosoma haematobium/aislamiento & purificación , Animales , Adolescente , Erradicación de la Enfermedad , Adulto Joven , Preescolar , Persona de Mediana Edad , Tanzanía/epidemiología , Encuestas y Cuestionarios , Esquistosomiasis/diagnóstico , Esquistosomiasis/epidemiología , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis/prevención & control , Conocimientos, Actitudes y Práctica en Salud , Anciano , Personal de SaludRESUMEN
Schistosomiasis, caused by Schistosoma trematodes, is a significant global health concern, particularly affecting millions in Africa and Southeast Asia. Despite efforts to combat it, the rise of praziquantel (PZQ) resistance underscores the need for new treatment options. Protein kinases (PKs) are vital in cellular signaling and offer potential as drug targets. This study focused on focal adhesion kinase (FAK) as a candidate for anti-schistosomal therapy. Transcriptomic and proteomic analyses of adult S. mekongi worms identified FAK as a promising target due to its upregulation and essential role in cellular processes. Molecular docking simulations assessed the binding energy of FAK inhibitors to Schistosoma FAK versus human FAK. FAK inhibitor 14 and PF-03814735 exhibited strong binding to Schistosoma FAK with minimal binding for human FAK. In vitro assays confirmed significant anti-parasitic activity against S. mekongi, S. mansoni, and S. japonicum, comparable to PZQ, with low toxicity in human cells, indicating potential safety. These findings highlight FAK as a promising target for novel anti-schistosomal therapies. However, further research, including in vivo studies, is necessary to validate efficacy and safety before clinical use. This study offers a hopeful strategy to combat schistosomiasis and reduce its global impact.
Asunto(s)
Proteómica , Schistosoma , Esquistosomiasis , Transcriptoma , Animales , Humanos , Proteómica/métodos , Schistosoma/efectos de los fármacos , Schistosoma/genética , Schistosoma/metabolismo , Esquistosomiasis/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Proteínas del Helminto/metabolismo , Proteínas del Helminto/genética , Perfilación de la Expresión Génica/métodos , Inhibidores de Proteínas Quinasas/farmacología , Proteoma/metabolismoRESUMEN
One Health surveillance involves the analysis of human, animal and environmental samples, recognising their interconnectedness in health systems. Such considerations are crucial to investigate the transmission of many pathogens, including drug-resistant bacteria and parasites. The highest rates of antimicrobial resistance (AMR)-associated deaths are observed in sub-Saharan Africa, where concurrently the waterborne parasitic disease schistosomiasis can be highly endemic in both humans and animals. Although there is growing acknowledgment of significant interactions between bacteria and parasites, knowledge of relationships between schistosomes, microbes and AMR remains inadequate. In addition, newly emergent research has revealed the previously underappreciated roles of animals and the environment in both AMR and schistosomiasis transmission. We consider shared environmental drivers and colonisation linkage in this narrative review, with a focus on extended-spectrum beta-lactamase-mediated resistance among bacteria from the Enterobacteriaceae family, which is exceedingly prevalent and responsible for a high burden of AMR-associated deaths. Then we examine novel findings from Malawi, where the landscapes of AMR and schistosomiasis are rapidly evolving, and make comparisons to other geographic areas with similar co-infection epidemiology. We identify several knowledge gaps that could be addressed in future research, including the need to characterise the impact of intestinal schistosomiasis and freshwater contact on intestinal AMR colonisation, before proposing a rationale for connecting AMR surveillance and schistosomiasis research within a One Health framework.
Asunto(s)
Salud Única , Esquistosomiasis , Humanos , Esquistosomiasis/epidemiología , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis/transmisión , Animales , Malaui/epidemiología , Enterobacteriaceae/efectos de los fármacos , Schistosoma/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Infecciones por Enterobacteriaceae/epidemiologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Schistosomiasis, caused by infection with organisms of the Schistoma genus, is a parasitic and infectious disease that poses a significant risk to human health. Schistosomiasis has been a widespread issue in China for at least 2000 years. Traditional Chinese medicine (TCM) has a rich history of treating this disease, and the significant theoretical and practical knowledge attained therein may be useful in modern practice. AIM OF THE STUDY: To comprehensively review TCM for the treatment of schistosomiasis, summarize the molecular basis, mechanism of action, active ingredients and formulas of TCM, and clarify the value of TCM for expanding drug options for the clinical treatment of schistosomiasis. MATERIALS AND METHODS: In PubMed, Web of Science, ScienceDirect, Google Scholar and CNKI databases, "Schistosomiasis", "Schistosoma mansoni", "Schistosoma japonicum", "Liver fibrosis" and "Granuloma" were used as the key words. Information related to in vivo animal studies and clinical studies of TCM for the treatment of schistosomiasis in the past 25 years was retrieved, and the inclusion criteria focused on medicinal plants that had a history of use in China. RESULTS: In this study, we collected and organized a large amount of literature on the treatment of schistosomiasis by TCM. TCM exerts therapeutic effects through antischistosomal and immunomodulatory effects, suppresses HSC activation and proliferation, reduces ECM deposition, and inhibits oxidative stress and other activities. The treatment of schistosomiasis by TCM has a unique advantage, especially for the treatment of schistosomal liver fibrosis, and the treatment of schistosomiasis with TCM in combination with praziquantel is superior to monotherapy. CONCLUSION: Schistosomiasis remains a global public health problem, and TCM has made significant progress in the prevention and treatment of schistosomiasis and is a potential source of drugs for the treatment of schistosomiasis. However, research on drug screening and the mechanism of action of TCM for the treatment of schistosomiasis is lacking, and further studies and research are needed.
Asunto(s)
Medicamentos Herbarios Chinos , Medicina Tradicional China , Esquistosomiasis , Medicina Tradicional China/métodos , Humanos , Animales , Esquistosomiasis/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacologíaRESUMEN
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.
Asunto(s)
Diseño de Fármacos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Relación Estructura-Actividad Cuantitativa , Schistosoma mansoni , Esquistosomiasis , Schistosoma mansoni/efectos de los fármacos , Ligandos , Animales , Esquistosomiasis/tratamiento farmacológico , NADH NADPH Oxidorreductasas/antagonistas & inhibidores , NADH NADPH Oxidorreductasas/química , NADH NADPH Oxidorreductasas/metabolismo , Humanos , Complejos MultienzimáticosRESUMEN
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 Schistosoma species, due to reports of reduced efficacy and resistance. Therefore, this study seeks to investigate the antischistosomal potential of phytochemicals from Azadirachta indica 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 A. indica 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 (Schistosoma mansoni 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 Azadirachta indica could serve as a potential lead compound for the development of an anti-schistosomal drug.
Asunto(s)
Azadirachta , Dihidroorotato Deshidrogenasa , Simulación del Acoplamiento Molecular , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Esquistosomiasis , Azadirachta/química , Animales , Esquistosomiasis/tratamiento farmacológico , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/antagonistas & inhibidores , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/metabolismo , Humanos , Fitoquímicos/farmacología , Fitoquímicos/química , Simulación de Dinámica Molecular , Schistosoma mansoni/efectos de los fármacos , Schistosoma mansoni/enzimología , NADH NADPH Oxidorreductasas/antagonistas & inhibidores , NADH NADPH Oxidorreductasas/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Simulación por Computador , Esquistosomicidas/farmacología , Esquistosomicidas/química , Esquistosomicidas/uso terapéutico , Complejos Multienzimáticos/antagonistas & inhibidores , Complejos Multienzimáticos/metabolismo , Praziquantel/farmacología , Praziquantel/química , Praziquantel/uso terapéuticoRESUMEN
BACKGROUND: Soil-transmitted helminthiasis (STH) and schistosomiasis (SCH) are among the most prevalent neglected tropical diseases (NTDs), affecting 1.5 billion globally, with a significant burden in sub-Saharan Africa, particularly Nigeria. These diseases impair health and contribute to socio-economic challenges, especially in children, undermining educational and future economic prospects. The 2030 NTD Roadmap highlights Mass Drug Administration (MDA) as a critical strategy for controlling these NTDs, targeting vulnerable populations like school-age children. Despite some successes, challenges persist, indicating the need for deeper insights into program implementation. This study focuses on the perspectives of health workers implementing MDA in selected local government areas (LGAs) of Ogun State, Nigeria, aiming to identify challenges and enablers that align with the broader NTD 2030 goals. METHODOLOGY/PRINCIPAL FINDINGS: The study used a qualitative research approach involving focus group discussions and in-depth interviews with health workers engaged in neglected tropical disease control programs in Ogun State, Nigeria, between July and September 2022. A semi-structured questionnaire guided the exploration of ideas, and the data were analyzed using the QRS Nvivo 12 software package. The study found that the school-based MDA control program's efficacy largely relies on strong collaborations and partnerships, particularly with educators, community heads, and other stakeholders. These alliances and strategic communication methods, like town announcements and media campaigns, have been pivotal in reaching communities. However, the program does grapple with hurdles such as parental misconceptions, limited funds, insufficient staffing, and misalignment with the Ministry of Education. It is recommended to boost funding, foster early stakeholder involvement, enhance mobilization techniques, and consider introducing a monitoring card system similar to immunization. CONCLUSIONS/SIGNIFICANCE: The MDA Integrated Control Programs for STH and SCH in Ogun State schools demonstrate a holistic approach, integrating knowledge, collaboration, communication, and feedback. Health workers have shown commitment and adeptness in their roles. However, achieving maximum efficacy requires addressing critical barriers, such as parental misconceptions and funding challenges. Adopting the recommended strategies, including proactive communication, increased remuneration, and introducing a tracking system, can significantly enhance the program's reach and impact. The involvement of all stakeholders, from health workers to community leaders and parents, is essential for the program's sustainability and success.
Asunto(s)
Personal de Salud , Helmintiasis , Administración Masiva de Medicamentos , Esquistosomiasis , Suelo , Humanos , Nigeria/epidemiología , Esquistosomiasis/prevención & control , Esquistosomiasis/epidemiología , Esquistosomiasis/tratamiento farmacológico , Helmintiasis/prevención & control , Helmintiasis/epidemiología , Helmintiasis/tratamiento farmacológico , Suelo/parasitología , Masculino , Femenino , Instituciones Académicas , Adulto , Enfermedades Desatendidas/prevención & control , Enfermedades Desatendidas/epidemiología , Niño , Antihelmínticos/uso terapéutico , Antihelmínticos/administración & dosificación , Grupos FocalesRESUMEN
BACKGROUND: Hundreds of millions of doses of Praziquantel (PZQ) have been administered to persons with and without schistosomiasis living in schistosomiasis endemic settings, through the mass drug administration (MDA) strategy which started in the early 2000s. A recent publication suggested high risk of PZQ-related visual disorders, raising public health concerns. We aim to systematically synthesize evidence on the magnitude of PZQ-related visual disorders. METHODS: We will search PubMed, Google Scholar, CINAHL, SCOPUS, CENTRAL and LILACS from 1977 (when the first human clinical trials on PZQ started) to 31st May 2024, with no language restrictions. The key search terms will include "Praziquantel", "PZQ", "visual disorder", "adverse events", "side effects", "blurry vision" and "visual impairment" together with alternative terms and synonyms. All the countries endemic for schistosomiasis will be included as search terms. We will also search HINARI, Africa Journals Online, Thesis Databases and Preprint Repositories. Where necessary, we will contact expert researchers working in the field of schistosomiasis, UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), pharmaceutical industries, country-specific Food and Drug Authorities (FDAs) and the European Medicines Agency databases. We will search Conference Proceedings and reference lists of relevant studies for additional studies. At least two authors will independently select studies, extract data and assess risk of bias in the included studies. Any disagreements or discrepancies will be resolved through discussion between the reviewers. Heterogeneity will be explored graphically, and statistically using the I2-statistic. We will conduct random-effects meta-analysis when heterogeneity is appreciable, and express dichotomous outcomes (visual adverse events including excessive lacrimation, blurry vision and visual impairments) as risk ratio (RR) or Odds Ratio (OR) with their 95% confidence interval (CI). We will perform subgroup analysis to assess the impact of heterogeneity, and sensitivity analyses to test the robustness of the effect estimates. The overall level of evidence will be assessed using GRADE. EXPECTED OUTCOMES: The present review expects to identify and categorize visual disorders occurring after administration of PZQ, alone or in combination with other drugs. By synthesizing the data from multiple studies, the review aims to present a quantitative assessment of the risk or odds of experiencing a visual disorder in different populations after ingesting PZQ. The review will also generate insights into whether PZQ in combination with other drugs are associated with increased odds of visual disorders and whether the occurrence of visual disorders correlates with dosage or treatment duration. Policymakers, public health experts and stakeholders could rely on the review findings to deliver context-sensitive preventive chemotherapy programs by adjusting drug combinations or dosing schedules to reduce risk of visual adverse effects in populations treated with PZQ. The review aims to identify gaps in the current evidence regarding visual disorders following PZQ administration in schistosomiasis endemic settings which can serve as the basis for future research on important but unanswered questions. DISSEMINATION AND PROTOCOL REGISTRATION: The findings of this study will be disseminated through stakeholder forums, conferences, and peer-review publications. The review protocol has been registered in the International Prospective Register for Systematic Reviews (PROSPERO)- CRD42023417963.
Asunto(s)
Administración Masiva de Medicamentos , Praziquantel , Esquistosomiasis , Revisiones Sistemáticas como Asunto , Trastornos de la Visión , Humanos , Esquistosomiasis/epidemiología , Esquistosomiasis/prevención & control , Esquistosomiasis/tratamiento farmacológico , Praziquantel/uso terapéutico , Praziquantel/efectos adversos , Praziquantel/administración & dosificación , Trastornos de la Visión/epidemiología , Trastornos de la Visión/inducido químicamente , Metaanálisis como Asunto , Enfermedades Endémicas/prevención & control , Antihelmínticos/uso terapéutico , Antihelmínticos/administración & dosificación , Antihelmínticos/efectos adversosAsunto(s)
Enfermedades Testiculares , Humanos , Masculino , Enfermedades Testiculares/diagnóstico por imagen , Enfermedades Testiculares/patología , Enfermedades Testiculares/diagnóstico , Esquistosomiasis/diagnóstico , Esquistosomiasis/tratamiento farmacológico , Antihelmínticos/uso terapéutico , Praziquantel/uso terapéutico , AdultoRESUMEN
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 budget allocation 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.
Asunto(s)
Antihelmínticos , Helmintiasis , Administración Masiva de Medicamentos , Esquistosomiasis , Suelo , Humanos , Nigeria/epidemiología , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis/epidemiología , Esquistosomiasis/prevención & control , Helmintiasis/tratamiento farmacológico , Helmintiasis/epidemiología , Helmintiasis/prevención & control , Niño , Suelo/parasitología , Antihelmínticos/uso terapéutico , Antihelmínticos/administración & dosificación , Femenino , Masculino , Adolescente , Praziquantel/uso terapéutico , Praziquantel/administración & dosificación , Mebendazol/uso terapéutico , Mebendazol/administración & dosificaciónRESUMEN
Objective: To determine if the prevalence of schistosomiasis in children aged 9-12 years is associated with the prevalence in 5-8-year-olds and adults after preventive chemotherapy in schools or the community. Methods: We combined data from four community-randomized, preventive chemotherapy trials in treatment-naïve populations in Côte d'Ivoire, Kenya and the United Republic of Tanzania during 2010-2016 according to the number of praziquantel treatments and the delivery method. Schistosoma mansoni infection was sought on two slides prepared from each participant's first stool using the Kato-Katz technique. We assessed associations between S. mansoni prevalence in 9-12-year-olds and 5-8-year-olds and adults in the community before and after treatment using Bayesian regression models. Findings: Stool samples from 47 985 5-8-year-olds, 81 077 9-12-year-olds and 20 492 adults were analysed. We found associations between the prevalence in 9-12-year-olds and that in 5-8-year-olds and adults after preventive treatment, even when only school-age children were treated. When the prevalence in 9-12-year-olds was under 10%, the prevalence in 5-8-year-olds was consistently under 10%. When the prevalence in 9-12-year-olds was under 50%, the prevalence in adults after two or four rounds of preventive chemotherapy was 10%-15% lower than before chemotherapy. Post-chemotherapy age-group associations were consistent with pre-chemotherapy associations in this analysis and previous studies. Conclusion: The prevalence of S. mansoni infection in 9-12-year-olds was associated with the prevalence in other age groups and could be used to guide community treatment decisions.
Asunto(s)
Esquistosomiasis , Niño , Adulto , Humanos , Côte d'Ivoire/epidemiología , Prevalencia , Teorema de Bayes , Kenia/epidemiología , Tanzanía/epidemiología , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis/epidemiología , HecesRESUMEN
INTRODUCTION: Schistosomiasis is a parasitic infection highly prevalent in sub-Saharan Africa (SSA) with Madagascar being among the countries with highest burden of the disease worldwide. Despite WHO recommendations, suggesting treatment of pregnant women after the first trimester, this group is still excluded from Mass Drug Administration programs. Our study, had the objective to measure the prevalence of schistosome infection among pregnant women in Madagascar in order to inform public health policies for treatment in this vulnerable population. METHODS: Women were recruited for this cross-sectional study between April 2019 and February 2020 when attending Antenatal Care Services (ANCs) at one of 42 included Primary Health Care Centers. The urine-based upconverting reporter particle, lateral flow (UCP-LF) test detecting circulating anodic antigen was used for the detection of schistosome infections. To identify factors associated with the prevalence of schistosome infection crude and adjusted prevalence ratios and 95% CIs were estimated using mixed-effect Poisson regression. RESULTS: Among 4,448 participating women aged between 16 and 47 years, the majority (70.4%, 38 n = 3,133) resided in rural settings. Overall, the prevalence of schistosome infection was 55.9% (n = 2486, CI 95%: 53.3-58.5). A statistically significant association was found with age group (increased prevalence in 31-47 years old, compared to 16-20 years old (aPR = 1.15, CI 95%: 1.02-1.29) and with uptake of antimalaria preventive treatment (decreased prevalence, aPR = 0.85, CI 95%: 0.77-0.95). No other associations of any personal characteristics or contextual factors with schistosome infection were found in our multivariate regression analysis. DISCUSSION AND CONCLUSION: The high prevalence of schistosome infection in pregnant women supports the consideration of preventive schistosomiasis treatment in ANCs of the Malagasy highlands. We strongly advocate for adapting schistosomiasis programs in highly endemic contexts. This, would contribute to both the WHO and SDGs agendas overall to improving the well-being of women and consequently breaking the vicious cycle of poverty perpetuated by schistosomiasis.