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ACS Omega Jun 2024Chikungunya virus (CHIKV) has been reported in over 120 countries and is the causative agent of Chikungunya fever. The debilitating nature of this disease, which can...
Chikungunya virus (CHIKV) has been reported in over 120 countries and is the causative agent of Chikungunya fever. The debilitating nature of this disease, which can persist months to years after acute infection, drastically impacts the quality of life of patients. Yet, specific antivirals are lacking for the treatment of this disease, which makes the search for new drugs necessary. In this context, the nsP2 protease emerges as an attractive therapeutic target, and drug repurposing strategies have proven to be valuable. Therefore, we combined in silico and in vitro methods to identify known drugs as potential CHIKV nsP2 protease inhibitors with antiviral properties within DrugBank. Herein, we developed a hybrid virtual screening pipeline comprising pharmacophore- and target-based screening, drug-like, and pharmaceutical filtering steps. Six virtual hits were obtained, and two of them, capecitabine (CPB) and oxibendazole (OBZ), were evaluated against CHIKV replication in Vero cells. CPB did not present antiviral activity, whereas OBZ inhibited the replication of two different strains of CHIKV, namely, 181-25 (Asian genotype) and BRA/RJ/18 (clinical isolate from ECSA genotype). OBZ showed potent antiviral activity against the CHIKV BRA/RJ/18 (EC = 11.4 μM) with a high selectivity index (>44). Analogs of OBZ (albendazole, fenbendazole, and mebendazole) were also evaluated, but none exhibited anti-CHIKV activity, and further, their stereoelectronic features were analyzed. Additionally, we observed that OBZ acts mainly at post-entry steps. Hence, our results support further in vivo studies to investigate the antiviral potential of OBZ, which offers a new alternative to fight CHIKV infections.
PubMed: 38947813
DOI: 10.1021/acsomega.4c03417 -
Pharmaceuticals (Basel, Switzerland) May 2024Mebendazole () is a benzimidazole carbamate anthelmintic used worldwide for the treatment and prevention of parasitic disorders in animals and humans. A large number of...
Mebendazole () is a benzimidazole carbamate anthelmintic used worldwide for the treatment and prevention of parasitic disorders in animals and humans. A large number of in vivo and in vitro studies have demonstrated that also has anticancer activity in multiple types of cancers. After oral administration, the phenylketone moiety of is rapidly reduced to the hydroxyl group to form the chiral hydroxy metabolite (). To the best of our knowledge, there is no information in the literature on the stereochemical course of transformation and the anthelmintic and antitumor activity of individual enantiomers of . In the present study, we describe in detail the direct HPLC resolution of on a 100 mm × 4.6 mm Chirapak IG-3 column packed with 3 μm silica particles containing amylose (3-chloro-5-methylphenylcarbamate) as a selector. At 25 °C and using pure methanol as the mobile phase, the enantioseparation and resolution factors were 2.38 and 6.13, respectively. These conditions were scaled up at a semi-preparative scale using a 250 mm × 10 mm Chiralpak IG column to isolate multi-milligram amounts of both enantiomeric forms of the chiral metabolite. The chiroptical properties of the collected enantiomers were determined and, through a theoretical study, were related to the more stable conformations of MBZ-OH. The first and second eluted enantiomers were dextrorotatory and levorotatory, respectively, in dimethylformamide solution. Finally, by recording the retention factors of the enantiomers as the water content in the water-acetonitrile mobile phases was progressively varied, U-shaped retention maps were generated, indicating a dual and competitive hydrophilic interaction liquid chromatography and reversed-phase liquid chromatography retention mechanism on the Chirapak IG-3 chiral stationary phase.
PubMed: 38931363
DOI: 10.3390/ph17060696 -
BMJ Case Reports Jun 2024Rarer causes of acute pancreatitis may be considered in certain settings, such as parasitism in endemic regions. This report describes a pregnant female (second...
Rarer causes of acute pancreatitis may be considered in certain settings, such as parasitism in endemic regions. This report describes a pregnant female (second trimester) in her 20s who presented with 3-day steady epigastric pain radiating to the back and passage of worm from the mouth. She was diagnosed with mild acute pancreatitis, given a significantly elevated serum lipase and absence of organ failures. Fecalysis showed ova; hence, she was treated with mebendazole. Plain MR cholangiopancreatography showed an 842 mL necrotic pancreatic fluid collection and tubular flow void foci within the gallbladder and duodenum consistent with helminthiasis. The patient was managed conservatively in the absence of indications for drainage. The abdominal pain remarkably improved, and she underwent eventual vacuum-assisted delivery to a healthy term baby 4 months after the bout of acute pancreatitis.
Topics: Humans; Female; Ascariasis; Pregnancy; Pancreatitis, Acute Necrotizing; Animals; Ascaris lumbricoides; Pregnancy Complications, Parasitic; Adult; Mebendazole; Abdominal Pain; Cholangiopancreatography, Magnetic Resonance
PubMed: 38862191
DOI: 10.1136/bcr-2024-260316 -
Frontiers in Pharmacology 2024Autosomal dominant polycystic kidney disease (ADPKD) is a rare genetic disorder characterised by numerous renal cysts, the progressive expansion of which can impact...
Autosomal dominant polycystic kidney disease (ADPKD) is a rare genetic disorder characterised by numerous renal cysts, the progressive expansion of which can impact kidney function and lead eventually to renal failure. Tolvaptan is the only disease-modifying drug approved for the treatment of ADPKD, however its poor side effect and safety profile necessitates the need for the development of new therapeutics in this area. Using a combination of transcriptomic and machine learning computational drug discovery tools, we predicted that a number of existing drugs could have utility in the treatment of ADPKD, and subsequently validated several of these drug predictions in established models of disease. We determined that the anthelmintic mebendazole was a potent anti-cystic agent in human cellular and models of ADPKD, and is likely acting through the inhibition of microtubule polymerisation and protein kinase activity. These findings demonstrate the utility of combining computational approaches to identify and understand potential new treatments for traditionally underserved rare diseases.
PubMed: 38846086
DOI: 10.3389/fphar.2024.1397864 -
Clinical Case Reports May 2024Here we present a case of a 4-year-old girl who suffered from vulvovaginitis caused by . All members of her family were also infected by this helminth. Treatment with...
KEY CLINICAL MESSAGE
Here we present a case of a 4-year-old girl who suffered from vulvovaginitis caused by . All members of her family were also infected by this helminth. Treatment with mebendazole was administered to all family members and it was found that the entire family had been cured.
ABSTRACT
Vulvovaginitis, an inflammation of the vulvovaginal mucous membranes, is a common reason for pediatric gynecology consultations. One of the causes of this condition is a parasitic worm known as (). In girls, adult worms can infiltrate the vagina and release eggs, leading to the development of vulvovaginitis. Furthermore, these worms have the ability to invade the endometrial cavity too. Here we present a case of a 4-year-old girl who suffered from vulvovaginitis caused by . All members of her family were also infected by this parasitic helminth. In the vaginal sample, apart from the eggs, the female adult worm was observed under the microscope. Treatment with mebendazole was administered to all family members, and their progress was followed for a period of 3 weeks, during which it was found that the entire family had been cured. This patient experienced significant improvement in symptoms related to severe anxiety, nervousness, vaginal inflammation, itching, and vulvovaginitis caused by . To prevent infection by , it is crucial to disinfect underwear and bed sheets. In kindergartens, the spread of this parasite should not be underestimated, and asymptomatic individuals who have been exposed to infected persons should receive treatment to prevent an epidemic. Maintaining cleanliness and hygiene, especially after using the toilet, is of the most importance, particularly for girls who are more susceptible to infection. Additionally, it is essential for all family members to be aware of the transmission routes of this parasite.
PubMed: 38725928
DOI: 10.1002/ccr3.8902 -
Journal of Epidemiology and Global... May 2024Soil-transmitted helminthic (STH) infections are the leading cause of stunting among children. To lessen the burden, the World Health Organization (WHO) recommended a...
BACKGROUND
Soil-transmitted helminthic (STH) infections are the leading cause of stunting among children. To lessen the burden, the World Health Organization (WHO) recommended a periodic deworming program through the use of single-dose therapy in the endemic regions. Therefore, the purpose of this study was to synthesize evidence about the efficacy of anthelminthic drugs against STH infections among preschool and school-age children.
METHODS
The Preferred Reposting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were followed in this study. Relevant electronic databases, including PubMed, Scopus, Embase, DOAJ, Science Direct, the WHO Clinical Trials.gov library, Google Scholar, and AJOL databases, were searched for relevant publications. Randomized controlled trials (RCTs) and non-randomized interventional studies focused on the efficacy of albendazole and mebendazole against STHs in children were included in the study. Review Manager was used to analyze the data. A random effects model was used to obtain the pooled estimated efficacy. To evaluate heterogeneity, the I test and Cochrane Q (χ) were employed. The risk of publication bias was investigated using Egger's test and the funnel plot. The protocol of this review was registered at the PROSPERO international prospective register of systematic reviews (CRD42023401196).
RESULTS
Of the 69 publications selected for the systematic review, 66 with complete data were included in the meta-analysis. Single doses of albendazole and mebendazole have shown satisfactory efficacy [egg reduction rate (ERR)] against Ascaris lumbricoides [95.54% (95% CI: 88.75-102.34%) and 98.69% (95% CI: 97.68-99.65%), respectively. The effectiveness of these two drugs against Trichuris trichiura and hookworms was comparatively low (< 80% ERR), except for albendazole, which showed high ERRs [93.44% (95%CI: 92.39-94.49%)] against hookworms. The cure rate (CR) of albendazole against T. trichiura, A. lumbricoides, and hookworms were 50.8%, 91.3%, and 78.32%, respectively. Likewise, mebendazole showed CRs of 48.15%, 92.8%, and 49.32% against T. trichiura, A. lumbricoides, and hookworms, respectively. Subgroups such as studies conducted after 2000, diagnostic type (McMaster), and longer follow-up weeks significantly reduced the efficacy of the two drugs against T. trichura. While the combination of albendazole or mebendazole with other drugs and RCT showed significantly improved efficacy against T. trichura. The count of eggs per gram of stool (EPG) was identified as one of the variables that negatively and significantly influenced the efficacy of albendazole or mebendazole against A. lumbricoides.
CONCLUSION
Despite the wide range of ERRs and CR reported in the different articles included in this review, the pooled estimated efficacy of albendazole and mebendazole against STHs falls in the satisfactory category of WHO recommendations. Further evaluation of the combination of anthelminthic drugs as a preventive chemotherapy option and routine drug efficacy testing are necessary to prevent the emergence and widespread use of drug-resistant STHs.
PubMed: 38696109
DOI: 10.1007/s44197-024-00231-7 -
BMC Women's Health Apr 2024Enterobius vermicularis (E. vermicularis), also referred to as pinworm, is a widespread human intestinal parasite which predominantly occurs in young children, making...
BACKGROUND
Enterobius vermicularis (E. vermicularis), also referred to as pinworm, is a widespread human intestinal parasite which predominantly occurs in young children, making their caretakers a population at risk for the transmission of this helminth. It can occasionally affect extraintestinal organs and tissues, including the female genital tract. Infestation can be asymptomatic or manifest as different kinds of gynaecological disorders, such as pelvic inflammation mimicking tumours, abnormal uterine bleeding, or vaginitis. Diagnosis is made by identifying ova in the sample collected from the perineal skin using a transparent adhesive tape or microscopic examination of resected tissue. Mebendazole is the first-line medication and should also be administered to all household members.
CASE PRESENTATION
We present a case of a patient who had undergone surgery for invasive cervical cancer with an accidental finding of E. vermicularis eggs in the cervix.
CONCLUSIONS
Although not very common, infestation with E. vermicularis should be considered in differential diagnoses of various gynaecological disorders accompanied by histological findings of granulomatous inflammation.
Topics: Humans; Female; Enterobiasis; Uterine Cervical Neoplasms; Enterobius; Animals; Mebendazole; Cervix Uteri; Diagnosis, Differential; Middle Aged; Adult
PubMed: 38678281
DOI: 10.1186/s12905-024-03073-4 -
Animals : An Open Access Journal From... Apr 2024The production of small ruminant autochthonous breeds in the Centre region of Portugal is practiced in a semi-extensive husbandry system, exposing animals to parasitic...
The production of small ruminant autochthonous breeds in the Centre region of Portugal is practiced in a semi-extensive husbandry system, exposing animals to parasitic infections. The main objective of this study was to estimate the prevalence of lungworm infection and identify risk factors. Fecal samples of 203 goats and 208 sheep from 30 herds were collected and subjected to the modified Baermann test. The overall prevalence of infection was 57.7%, significantly higher in goats (95.6%) than in sheep (20.7%) ( < 0.001). According to the binary logistic regression model, sheep dewormed with albendazole, mebendazole plus closantel, or ivermectin plus clorsulon presented a risk of Protostrongylidae infection 29.702, 7.426, or 8.720 times higher, respectively, than those dewormed with eprinomectin. Additionally, the presence of gastrointestinal parasites was investigated in 307 fecal samples using Mini-FLOTAC. The overall prevalence of infection was 86.3%, also significantly higher in goats (93.2%) than in sheep (79.9%) ( < 0.001). Strongyle-type eggs were the most frequently identified, both in sheep (69.8%) and goats (87.8%), followed by oocysts (40.3% in sheep and 68.9% in goats). Considering the high prevalence and the burden of lungworm parasitic infection, it is urgent to determine its economic impact and the repercussions in animal health in the Centre region of Portugal to establish appropriate therapeutic guidelines.
PubMed: 38672389
DOI: 10.3390/ani14081241 -
Helminthologia Mar 2024To treat and control parasitic infections, traditional medical remedies using plant products are utilized as antiparasitic agents rather than standard synthetic...
To treat and control parasitic infections, traditional medical remedies using plant products are utilized as antiparasitic agents rather than standard synthetic chemicals due to drug resistance. Myrrh, a resinous exudate of (Burseraceae), is a powerful antioxidant with a variety of medicinal uses. This study aimed to investigate the effect of the myrrh methanolic extract (MyE) of three concentrations (100, 50, and 25 mg/ml) on the sporulation of oocysts and as an anthelminthic effector via study. Characterization of the plant was done by Fourier-transform infrared spectroscopy (FT-IR). The earthworm, , is used as a model worm to evaluate the anthelminthic activity of MyE. -like oocysts are used as a model protozoan parasite in anticoccidial assays. The sporulation and inhibition (%) of -like were assessed by MyE compared to other chemical substances. FT-IR revealed the presence of twelve active compounds. Our results showed that paralysis and death of earthworms at MyE (100 mg/ml) were 7.88 ± 0.37 and 9.24 ± 0.60 min, respectively, which is more potency when compared to mebendazole (reference drug). In all treated worms, microscopic examinations revealed obvious surface architecture abnormality. This study shows that MyE affects oocysts sporulation in a dose-dependent manner. At 24 and 36 hr, a high concentration of MyE (100 mg/ml) inhibits sporulation by 90.95 and 87.17 %. At 36 hr, other concentrations of MyE (50 and 25 mg/ml), as well as amprolium, Dettol, and phenol inhibits oocyst sporulation by 40.17 %, 29.34 %, 45.09 %, 85.11 %, and 61.58 %, respectively. According to our research, the MyE extract had powerful anthelmintic and anticoccidial properties.
PubMed: 38659472
DOI: 10.2478/helm-2024-0008 -
Annals of Medicine and Surgery (2012) Apr 2024Hydatosis is a zoonotic parasitic disease caused by echinococcosis larval infection. South America, Africa, the Middle East, South Europe, India, and Australia are...
INTRODUCTION
Hydatosis is a zoonotic parasitic disease caused by echinococcosis larval infection. South America, Africa, the Middle East, South Europe, India, and Australia are endemic to this disease. Splenic involvement is a rare and complicated hydatid disease presentation. A splenic hydatid cyst is an infrequent clinical occurrence, even in regions where the disease is endemic.
CASE PRESENTATION
A 16-year-old male, having a background of mild abdominal trauma and non-resolving dull abdominal pain attended a paediatric surgical outpatient office and following a thorough examination, was diagnosed with a giant solitary isolated splenic hydatid cyst. Subsequently, the patient received albendazole and underwent total splenectomy, necessitated by the considerable size of the cyst, classified as a giant.
CLINICAL DISCUSSION
Splenic involvement of hydatid disease is a rare presentation (0.5-8%.). With the initial clinical finding often involving the accidental discovery of a palpable mass, the most frequently reported symptoms and signs include the presence of a palpable mass, fever, dull pain, or splenomegaly. Ultrasound and computed tomography are the most helpful tools for evaluating focal splenic diseases. The preferred treatment involves the use of antihelminthic drugs such as albendazole or mebendazole in conjunction with splenectomy. Total splenectomy is the preferred approach and is associated with decreased hospital stay, reduced healthcare costs, and a lower likelihood of recurrence.
CONCLUSION
in endemic areas, in patients with splenic cysts, hydatidosis should be contemplated.
PubMed: 38576966
DOI: 10.1097/MS9.0000000000001851