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Bioinformatics and Biology Insights 2024Schistosomiasis, otherwise known as bilharzia or snail fever, is a disease that usually affects poor people and people exposed to poor sanitation. The disease affects...
Schistosomiasis, otherwise known as bilharzia or snail fever, is a disease that usually affects poor people and people exposed to poor sanitation. The disease affects over 200 million people worldwide annually. Schistosomiasis has been treated using a single drug, praziquantel, since the 1970s and this is resulting in schistosomes becoming resistant. Therefore, there is an urgent need to develop new antischistosoma drugs and vaccines. This study focuses on identifying potential antischistosomal compounds from the plant . We virtually screened a library of 163 compounds by docking against sulfotransferase (SULT) using the PyRx software. Docking scores ranged from -4.7 to -9.3 kcal/mol. Compounds with binding affinity of -7.6 or stronger were subjected to drug-likeness assessments using the DataWarrior software. We also employed the PAINS removal tool to filter off false-positive results. Twelve compounds passed the drug-likeness screen, and these were subjected to in silico toxicity predictions to determine their mutagenic, tumorigenic and reproductive potential. Seven compounds were predicted to be nontoxic. After considering the toxicity analysis results and drug scores of the compounds, we identified rosmarinic acid and hispidulin as qualifying for further evaluation as potential drugs against schistosomiasis. Free energy calculations using the fastDRH webserver and molecular dynamics simulations using CABS-flex showed that the receptor-ligand complexes for the 2 lead compounds are stable under physiological conditions. We recommend that rosmarinic acid and hispidulin be used as hit compounds for the development of potential antischistosomal drugs.
PubMed: 38550337
DOI: 10.1177/11779322241240651 -
PLoS Neglected Tropical Diseases Mar 2024Cystic Echinococcosis (CE) as a prevalent tapeworm infection of human and herbivorous animals worldwide, is caused by accidental ingestion of Echinococcus granulosus...
Cystic Echinococcosis (CE) as a prevalent tapeworm infection of human and herbivorous animals worldwide, is caused by accidental ingestion of Echinococcus granulosus eggs excreted from infected dogs. CE is endemic in the Middle East and North Africa, and is considered as an important parasitic zoonosis in Iran. It is transmitted between dogs as the primary definitive host and different livestock species as the intermediate hosts. One of the most important measures for CE control is dog deworming with praziquantel. Due to the frequent reinfection of dogs, intensive deworming campaigns are critical for breaking CE transmission. Dog reinfection rate could be used as an indicator of the intensity of local CE transmission in endemic areas. However, our knowledge on the extent of reinfection in the endemic regions is poor. The purpose of the present study was to determine E. granulosus reinfection rate after praziquantel administration in a population of owned dogs in Kerman, Iran. A cohort of 150 owned dogs was recruited, with stool samples collected before praziquantel administration as a single oral dose of 5 mg/kg. The re-samplings of the owned dogs were performed at 2, 5 and 12 months following initial praziquantel administration. Stool samples were examined microscopically using Willis flotation method. Genomic DNA was extracted, and E. granulosus sensu lato-specific primers were used to PCR-amplify a 133-bp fragment of a repeat unit of the parasite genome. Survival analysis was performed using Kaplan-Meier method to calculate cumulative survival rates, which is used here to capture reinfection dynamics, and monthly incidence of infection, capturing also the spatial distribution of disease risk. Results of survival analysis showed 8, 12 and 17% total reinfection rates in 2, 5 and 12 months following initial praziquantel administration, respectively, indicating that 92, 88 and 83% of the dogs had no detectable infection in that same time periods. The monthly incidence of reinfection in total owned dog population was estimated at 1.5% (95% CI 1.0-2.1). The results showed that the prevalence of echinococcosis in owned dogs, using copro-PCR assay was 42.6%. However, using conventional microscopy, 8% of fecal samples were positive for taeniid eggs. Our results suggest that regular treatment of the dog population with praziquantel every 60 days is ideal, however the frequency of dog dosing faces major logistics and cost challenges, threatening the sustainability of control programs. Understanding the nature and extent of dog reinfection in the endemic areas is essential for successful implementation of control programs and understanding patterns of CE transmission.
Topics: Humans; Dogs; Animals; Praziquantel; Iran; Reinfection; Farms; Echinococcosis; Echinococcus granulosus; Feces; Dog Diseases
PubMed: 38536863
DOI: 10.1371/journal.pntd.0011939 -
PLoS Neglected Tropical Diseases Mar 2024Female Genital Schistosomiasis (FGS) causes intravaginal lesions and symptoms that could be mistaken for sexually transmitted diseases or cancer. In adults, FGS lesions...
OBJECTIVE
Female Genital Schistosomiasis (FGS) causes intravaginal lesions and symptoms that could be mistaken for sexually transmitted diseases or cancer. In adults, FGS lesions [grainy sandy patches (GSP), homogenous yellow patches (HYP), abnormal blood vessels and rubbery papules] are refractory to treatment. The effect of treatment has never been explored in young women; it is unclear if gynaecological investigation will be possible in this young age group (16-23 years). We explored the predictors for accepting anti-schistosomal treatment and/or gynaecological reinvestigation in young women, and the effects of anti-schistosomal mass-treatment (praziquantel) on the clinical manifestations of FGS at an adolescent age.
METHOD
The study was conducted between 2011 and 2013 in randomly selected, rural, high schools in Ilembe, uThungulu and Ugu Districts, KwaZulu-Natal Province, East Coast of South Africa. At baseline, gynaecological investigations were conducted in female learners in grades 8 to 12, aged 16-23 years (n = 2293). Mass-treatment was offered in the low-transmission season between May and August (a few in September, n = 48), in accordance with WHO recommendations. Reinvestigation was offered after a median of 9 months (range 5-14 months). Univariate, multivariable and logistic regression analysis were used to measure the association between variables.
RESULTS
Prevalence: Of the 2293 learners who came for baseline gynaecological investigations, 1045 (46%) had FGS lesions and/or schistosomiasis, 209/1045 (20%) had GSP; 208/1045 (20%) HYP; 772/1045 (74%) had abnormal blood vessels; and 404/1045 (39%) were urine positive. Overall participation rate for mass treatment and gynaecological investigation: Only 26% (587/2293) learners participated in the mass treatment and 17% (401/2293) participated in the follow up gynaecological reinvestigations. Loss to follow-up among those with FGS: More than 70% of learners with FGS lesions at baseline were lost to follow-up for gynaecological investigations: 156/209 (75%) GSP; 154/208 (74%) HYP; 539/722 (75%) abnormal blood vessels; 238/404 (59%) urine positive. The grade 12 pupil had left school and did not participate in the reinvestigations (n = 375; 16%). Follow-up findings: Amongst those with lesions who came for both treatment and reinvestigation, 12/19 still had GSP, 8/28 had HYP, and 54/90 had abnormal blood vessels. Only 3/55 remained positive for S. haematobium ova. Factors influencing treatment and follow-up gynaecological investigation: HIV, current water contact, water contact as a toddler and urinary schistosomiasis influenced participation in mass treatment. Grainy sandy patches, abnormal blood vessels, HYP, previous pregnancy, current water contact, water contact as a toddler and father present in the family were strongly associated with coming back for follow-up gynaecological investigation. Challenges in sample size for follow-up analysis of the effect of treatment: The low mass treatment uptake and loss to follow up among those who had baseline FGS reduced the chances of a larger sample size at follow up investigation. However, multivariable analysis showed that treatment had effect on the abnormal blood vessels (adjusted odds ratio = 2.1, 95% CI 1.1-3.9 and p = 0.018).
CONCLUSION
Compliance to treatment and gynaecological reinvestigation was very low. There is need to embark on large scale awareness and advocacy in schools and communities before implementing mass-treatment and investigation studies. Despite challenges in sample size and significant loss to follow-up, limiting the ability to fully understand the treatment's effect, multivariable analysis demonstrated a significant treatment effect on abnormal blood vessels.
Topics: Adult; Pregnancy; Animals; Female; Adolescent; Humans; Praziquantel; South Africa; Schistosoma haematobium; Schistosomiasis haematobia; Genitalia, Female; Genital Diseases, Female; Water
PubMed: 38536861
DOI: 10.1371/journal.pntd.0011798 -
PLoS Neglected Tropical Diseases Mar 2024Schistosoma haematobium, the parasite that causes urogenital schistosomiasis, is widely prevalent in Tanzania. In addition to well-known effects on the urinary tract, S.... (Review)
Review
Schistosoma haematobium, the parasite that causes urogenital schistosomiasis, is widely prevalent in Tanzania. In addition to well-known effects on the urinary tract, S. haematobium also causes clinically- evident damage to the reproductive tract in approximately half of infected women, which is known as female genital schistosomiasis (FGS). FGS has major gynecologic and social consequences on women's reproductive health, yet little information is available regarding FGS in Tanzania. To cover that gap, we conducted the present scoping review to examine the epidemiology of FGS in Tanzania (both in the mainland and Zanzibar island) and to make recommendations for future work in this area. The available evidence from community-based and hospital-based retrospective studies indicates that FGS is a significant health problem in the country. Very few community-based studies have been reported from mainland Tanzania, and Zanzibar. Our review highlights the scarcity of efforts to address FGS in Tanzania and the need for additional community-based studies. The studies will help us understand the true burden of the disease nationwide, to assess the impact of praziquantel on FGS lesions, and to address social and mental health in relation to FGS. This review emphasizes integration of delivery of FGS related services in primary health care systems through the reproductive health clinics which covers sexually transmitted infections, HIV and cervical cancer screening. These actions are essential if this neglected gynecological disease is to be addressed in Tanzania.
Topics: Animals; Female; Humans; Tanzania; Public Health; Retrospective Studies; Early Detection of Cancer; Uterine Cervical Neoplasms; Genitalia, Female; Schistosomiasis haematobia; Schistosoma haematobium; Genital Diseases, Female
PubMed: 38466660
DOI: 10.1371/journal.pntd.0011954 -
Veterinarni Medicina Jan 2024Praziquantel (PZQ) is a drug effective against several parasitic diseases of fish caused by Platyhelminthes. The study assesses the efficacy of selected in-feed PZQ...
Praziquantel (PZQ) is a drug effective against several parasitic diseases of fish caused by Platyhelminthes. The study assesses the efficacy of selected in-feed PZQ doses in eliminating metacercariae in grass carp. The fish were infected with in laboratory conditions and subsequently treated with PZQ at daily doses of 30 (PZQ1), 50 (PZQ2), and 100 (PZQ3) mg/kg bw for seven days. The treatment trial was followed by a 23-day observation period during which the fish were parasitologically examined on days 0, 2, 8 and 23. Smaller fish were infected with a significantly higher ( < 0.05) number of metacercariae than bigger fish among three weight groups as follows: up to 7 g > 7 to 12 g > 12 g. The in-feed PZQ at doses of 30, 50 and 100 mg/kg bw for seven days was 47%, 84% and 88% effective against metacercariae , respectively. A significant decrease ( < 0.01) in moving and an increase ( < 0.01) in the immotile metacercariae in the eye's lens were recorded in all the trial groups on each sampling day. An increasing proportion of motile metacercariae in the post-treatment observation period was seen in PZQ2 and PZQ3, indicating a decreasing trend in the actual efficacy in an environment with no reinfection possibility.
PubMed: 38465001
DOI: 10.17221/97/2023-VETMED -
Frontiers in Epidemiology 2023The burden of schistosomiasis in Zambia has remained high over the years. The World Health Assembly recommended adequate mass drug administration coverage for...
The burden of schistosomiasis in Zambia has remained high over the years. The World Health Assembly recommended adequate mass drug administration coverage for schistosomiasis using Praziquantel chemotherapy for school-aged children and all at-risks adults. We aimed at investigating the coverage and the factors associated to the uptake for MDA for schistosomiasis in Ng'ombe township of Lusaka, Zambia. A cross-sectional survey was conducted in May and June 2021 phone calls to the residents of Ng'ombe township. Commcare software was used in the conduct of the survey. Pearson's Chi-square test and multiple logistic regression were conducted using the STATA version 15.0. 769 study participants were randomly selected using systematic sampling, of which 76.3% were younger than 40 years, 64.9% were female, 64.4% were married, 56.3% had reached the secondary educational level and 51.9% were employed. Coverage for MDA for schistosomiasis in Ng'ombe township in 2018 was found to be 49.8% (95% CI: 46.2%-53.4%). Positive predictors of the MDA were prior knowledge of the occurrence of the MDA in 2018 (aOR: 2.892, < 0.001) and believing that the provision of incentives like snacks was important during the MDA with PZQ in Ng'ombe township (aOR: 1.926, = 0.001), whereas age (aOR:0.979, = 0.009), marital status (aOR:0.620, = 0.006), employment status (aOR:0.587, = 0.001) were negative predictors of the MDA. Elimination of the burden of schistosomiasis in endemic settings needs the attainment of an optimum coverage and uptake during MDA with PZQ. Therefore, prior knowledge about an impending intervention and the provision of incentives like snacks during the intervention should be prioritized by MDA implementers, while background characteristics such as age, marital status, and employment status need to be taken into consideration when planning and promoting uptake in future MDAs.
PubMed: 38455938
DOI: 10.3389/fepid.2023.1168282 -
Journal of Taibah University Medical... Apr 2024Schistosomiasis, a neglected tropical disease, is a leading cause of mortality in affected geographic areas. Currently, because no vaccine for schistosomiasis is...
OBJECTIVES
Schistosomiasis, a neglected tropical disease, is a leading cause of mortality in affected geographic areas. Currently, because no vaccine for schistosomiasis is available, control measures rely on widespread administration of the drug praziquantel (PZQ). The mass administration of PZQ has prompted concerns regarding the emergence of drug resistance. Therefore, new therapeutic targets and potential compounds are necessary to combat schistosomiasis.
METHODS
Twenty-four potent derivatives of PZQ were optimized via density functional theory (DFT) at the B3LYP/6-31G∗ level. Quantitative structureactivity relationship (QSAR) models were generated and statistically validated, and a lead candidate was selected to develop therapeutic options with improved efficacy against schistosomiasis. The biological and binding energies of the designed compounds were evaluated. In addition, molecular dynamics; drug-likeness; absorption, distribution, metabolism, excretion, and toxicity (ADMET); and DFT studies were performed on the newly designed compounds.
RESULTS
Five QSAR models were generated, among which model 1 had favorable validation parameters (R: 0.957, R: 0.941, LOF: 0.101, Qcv: 0.906, and R: 0.783) and was chosen to identify a lead candidate. Other statistical parameters for the chosen model included variance inflation factor values ranging from 1.242 to 1.678, and a Y-scrambling coefficient (cRp) of 0.747. Five new compounds were designed with improved predicted activity (ranging from 5.081 to 7.022) surpassing those of both the lead compound and PZQ (predicted pEC of 5.545). Molecular dynamics simulation revealed high binding affinity of the proposed compounds toward the target receptor. ADMET and drug-likeness assessments indicated adherence to Lipinski's rule of five criteria, thereby suggesting pharmacological and oral safety. In addition, DFT analysis indicated resistance to electronic alteration during chemical reactions.
CONCLUSION
The proposed compounds exhibited potential drug characteristics, thus indicating their suitability for further investigation to enhance schistosomiasis treatment options.
PubMed: 38440085
DOI: 10.1016/j.jtumed.2024.02.003 -
Travel Medicine and Infectious Disease 2024
Topics: Humans; Schistosomiasis haematobia; Cystoscopy; Animals; Schistosoma haematobium; Urinary Tract Infections; Recurrence; Anthelmintics; Male; Female; Praziquantel; Adult
PubMed: 38423232
DOI: 10.1016/j.tmaid.2024.102702 -
PLoS Neglected Tropical Diseases Feb 2024Schistosomiasis is a major neglected parasitic disease that affects more than 240 million people worldwide caused by Platyhelminthes of the genus Schistosoma. The...
Schistosomiasis is a major neglected parasitic disease that affects more than 240 million people worldwide caused by Platyhelminthes of the genus Schistosoma. The treatment of schistosomiasis relies on the long-term application of a single safe drug, praziquantel (PZQ). Unfortunately, PZQ is very effective on adult parasites and poorly on larval stage and immature juvenile worms; this can partially explain the re-infection in endemic areas where patients are likely to host parasites at different developmental stages concurrently. Moreover, the risk of development of drug resistance because of the widespread use of a single drug in a large population is nowadays a serious threat. Hence, research aimed at identifying novel drugs to be used alone or in combination with PZQ is needed. Schistosomes display morphologically distinct stages during their life cycle and epigenetic mechanisms are known to play important roles in parasite growth, survival, and development. Histone deacetylase (HDAC) enzymes, particularly HDAC8, are considered valuable for therapeutic intervention for the treatment of schistosomiasis. Herein, we report the phenotypic screening on both larvae and adult Schistosoma mansoni stages of structurally different HDAC inhibitors selected from the in-house Siena library. All molecules have previously shown inhibition profiles on human HDAC6 and/or HDAC8 enzymes. Among them we identified a quinolone-based HDAC inhibitor, NF2839, that impacts larval and adult parasites as well as egg viability and maturation in vitro. Importantly, this quinolone-based compound also increases histone and tubulin acetylation in S. mansoni parasites, thus representing a leading candidate for the development of new generation anti-Schistosoma chemotherapeutics.
Topics: Animals; Humans; Anthelmintics; Histone Deacetylase 6; Larva; Praziquantel; Quinolones; Repressor Proteins; Schistosoma mansoni; Schistosomiasis; Schistosomiasis mansoni; Histone Deacetylase Inhibitors
PubMed: 38416775
DOI: 10.1371/journal.pntd.0011992 -
Parasite (Paris, France) 2024This clinical study assessed the efficacy of a topical combination of esafoxolaner, eprinomectin and praziquantel (NexGard Combo) in treating cats naturally infected...
This clinical study assessed the efficacy of a topical combination of esafoxolaner, eprinomectin and praziquantel (NexGard Combo) in treating cats naturally infected with the eyeworm Thelazia callipaeda (Nematoda, Thelaziidae). On Study Day (SD) 0, sixteen client-owned cats with eyeworm infection were allocated to an untreated control group (G1, 8 cats) or to a NexGard Combo treated group (G2, 8 cats) and subjected to ocular examination. Cats in G2 received the treatment as per label recommendations. On SD 7 and 14 (±1), cats were examined for the presence of eyeworms and clinical signs. On SD 14, eyeworms were collected and counted. On SD 7 and 14, all cats in G1 were still infected with eyeworms, while G2 cats were free from eyeworms on SD 7 and 14, demonstrating 100% efficacy (p < 0.0001). All collected eyeworms were morphologically and molecularly confirmed to be T. callipaeda. On SD 0, fifteen out of the sixteen cats (7 in G1 and 8 in G2) displayed inflammatory ocular signs. On SD 7, all eight untreated cats and seven treated cats displayed inflammatory ocular signs. On SD 14, five out of eight G2 treated cats had recovered, while the eight untreated cats still displayed inflammatory ocular signs. The treatment significantly reduced lacrimation and conjunctivitis (p = 0.0001). No adverse reactions occurred. This clinical study provides evidence that NexGard Combo is highly safe and effective for the treatment of T. callipaeda infection in cats under field conditions.
Topics: Humans; Cats; Animals; Praziquantel; Ivermectin; Thelazioidea; Isoxazoles; Naphthalenes
PubMed: 38415717
DOI: 10.1051/parasite/2024008