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1.
J Cell Mol Med ; 28(11): e18389, 2024 Jun.
Article En | MEDLINE | ID: mdl-38864691

Chemotherapy resistance remains a significant challenge in treating ovarian cancer effectively. This study addresses this issue by utilizing a dual drug-loaded nanomicelle system comprising albendazole (ABZ) and paclitaxel (PTX), encapsulated in a novel carrier matrix of D-tocopheryl polyethylene glycol 1000 succinate vitamin E (TPGS), soluplus and folic acid. Our objective was to develop and optimize this nanoparticulate delivery system using solvent evaporation techniques to enhance the therapeutic efficacy against ovarian cancer. The formulation process involved pre-formulation, formulation, optimization, and comprehensive characterization of the micelles. Optimization was conducted through a 32 factorial design, focusing on the effects of polymer ratios on particle size, zeta potential, polydispersity index (PDI) and entrapment efficiency (%EE). The optimal formulation demonstrated improved dilution stability, as indicated by a critical micelle concentration (CMC) of 0.0015 mg/mL for the TPGS-folic acid conjugate (TPGS-FOL). Extensive characterization included differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FTIR). The release profile exhibited an initial burst followed by sustained release over 90 h. The cytotoxic potential of the formulated micelles was superior to that of the drugs alone, as assessed by MTT assays on SKOV3 ovarian cell lines. Additionally, in vivo studies confirmed the presence of both drugs in plasma and tumour tissues, suggesting effective targeting and penetration. In conclusion, the developed TPGS-Fol-based nanomicelles for co-delivering ABZ and PTX show promising results in overcoming drug resistance, enhancing solubility, sustaining drug release, and improving therapeutic outcomes in ovarian cancer treatment.


Albendazole , Micelles , Ovarian Neoplasms , Paclitaxel , Female , Paclitaxel/pharmacology , Paclitaxel/administration & dosage , Paclitaxel/therapeutic use , Paclitaxel/chemistry , Albendazole/chemistry , Albendazole/pharmacology , Albendazole/administration & dosage , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Humans , Animals , Cell Line, Tumor , Drug Carriers/chemistry , Polyethylene Glycols/chemistry , Vitamin E/chemistry , Folic Acid/chemistry , Mice , Drug Liberation , Particle Size , Polyvinyls/chemistry , Polymers/chemistry , Xenograft Model Antitumor Assays
3.
PLoS One ; 19(5): e0303502, 2024.
Article En | MEDLINE | ID: mdl-38805475

BACKGROUND: Despite integrated prevention and control measures, the prevalence of hookworm is still high in Ethiopia. The re-infection rates and predictors are poorly addressed. Therefore, this study aimed to determine the patterns of hookworm re-infection rates and predictors among schoolchildren in northwest Ethiopia. METHODS: A prospective follow-up study was conducted among 86 schoolchildren from May to December 2022. Data on predictors was collected using a questionnaire. Stool samples were collected and processed via Kato-Katz, McMaster, and spontaneous tube sedimentation techniques. All hookworm-infected children were treated with albendazole and followed for six months. The re-infection rates of hookworm were checked in the 4th and 6th months. Data was entered into Epi-data version 3.1 and analysed using SPSS version 25. Descriptive statistics were used to compute the re-infection rate. The associations of predictors with hookworm re-infection rates were calculated by logistic regression. Variables with a p-value < 0.05 were considered statistically significant. RESULTS: Of the 86, 81 schoolchildren completed the study. The prevalence of hookworm re-infection in the 4th and 6th months was 23.5% and 33.3%, respectively. Living with family members greater than five (p = .017), poor utilization of latrine (p = .008), infrequent shoe wear (p = .039), and participating in irrigation (p = .020) were the predictors significantly associated with hookworm re-infections. CONCLUSIONS: The re-infection rate was high during the fourth and sixth months. Participating in irrigation, infrequent shoe wear, and poor latrine utilization were predictors of hookworm re-infection. Therefore, mass drug administration, regular shoe wearing, and health education should be advocated.


Albendazole , Hookworm Infections , Humans , Ethiopia/epidemiology , Child , Male , Female , Hookworm Infections/epidemiology , Prospective Studies , Albendazole/therapeutic use , Albendazole/administration & dosage , Prevalence , Reinfection/epidemiology , Adolescent , Feces/parasitology , Follow-Up Studies , Anthelmintics/therapeutic use , Anthelmintics/administration & dosage , Ancylostomatoidea/isolation & purification , Schools , Animals
4.
J Helminthol ; 98: e40, 2024 May 13.
Article En | MEDLINE | ID: mdl-38738533

In the past decade, interest has significantly increased regarding the medicinal and nutritional benefits of pomegranate (Punica granatum) peel. This study examined the effects of using pomegranate peel extract (PGE) alone and in combination with albendazole (ABZ) on ultrastructural and immunological changes in cystic echinococcosis in laboratory-infected mice. Results revealed that the smallest hydatid cyst size and weight (0.48 ± 0.47mm, 0.17 ± 0.18 gm) with the highest drug efficacy (56.2%) was detected in the PGE + ABZ group, which also exhibited marked histopathological improvement. Ultrastructural changes recorded by transmission electron microscopy including fragmentation of the nucleus, glycogen depletion, and multiple lysosomes in vacuolated cytoplasm were more often observed in PGE + ABZ group. IFN-γ levels were significantly increased in the group treated with ABZ, with a notable reduction following PGE treatment, whether administered alone or in combination with ABZ. Thus, PGE enhanced the therapeutic efficiency of ABZ, with improvement in histopathological and ultrastructural changes.


Albendazole , Echinococcosis , Plant Extracts , Pomegranate , Animals , Plant Extracts/pharmacology , Plant Extracts/administration & dosage , Pomegranate/chemistry , Mice , Echinococcosis/drug therapy , Echinococcosis/parasitology , Albendazole/pharmacology , Albendazole/administration & dosage , Anthelmintics/pharmacology , Anthelmintics/administration & dosage , Disease Models, Animal , Microscopy, Electron, Transmission , Interferon-gamma/blood , Female , Male
5.
Antimicrob Agents Chemother ; 68(5): e0121123, 2024 May 02.
Article En | MEDLINE | ID: mdl-38563751

Helminthiasis remains a public health issue in endemic areas. Various drugs have been proposed to improve efficacy against helminths. The study aimed to assess the safety and efficacy of three different anthelmintic combinations to treat Trichuris trichiura infections. We conducted a randomized assessors-blind clinical trial involving children aged 2-17 years with T. trichiura. Participants were randomly assigned to one of three treatment arms. On the first and third days, all participants got albendazole 400 mg, and on the second day, albendazole (arm A), mebendazole 500 mg (arm B), or pyrantel 125 mg/kg (arm C). We assessed treatment efficacy using the cure rate (CR) and egg reduction rate (ERR) at 3 and 6 weeks post-treatment. At 3 weeks post-treatment, ERR and CR were highest in study arm A [ERR = 94%, 95% confidence interval (CI): 92-95; CR = 71%; 95% CI: 58-81] compared to the B and C arms. Decrease in ERR was significant only for arm B versus arm A (P-value <0.001); decrease in ERR was significant for arms B and C (P-value <0.001). No statistical difference was observed in CR when comparing arms A and B (P-value =1.00) and C (P-value =0.27). At 6 weeks, a decrease in ERR was observed in three arms, significant only for arm C, 81% (95% CI: 78-83). A significant increase in egg counts was observed between 3 and 6 weeks post-treatment. All treatments were safe with mild adverse events. Albendazole 400 mg/day (arm A) showed the highest efficacy against trichuriasis. Nonetheless, this treatment regimen was able to cure half of the treated individuals highlighting concerns about controlling the transmission of T. trichiura.CLINICAL TRIALRegistered at ClinicalTrials.gov (NCT04326868).


Albendazole , Anthelmintics , Mebendazole , Pyrantel , Trichuriasis , Trichuris , Humans , Albendazole/therapeutic use , Albendazole/adverse effects , Albendazole/administration & dosage , Child , Mebendazole/therapeutic use , Trichuriasis/drug therapy , Male , Female , Trichuris/drug effects , Animals , Child, Preschool , Anthelmintics/therapeutic use , Anthelmintics/adverse effects , Anthelmintics/administration & dosage , Adolescent , Pyrantel/therapeutic use , Drug Therapy, Combination , Treatment Outcome , Parasite Egg Count
6.
Clin Infect Dis ; 78(Supplement_2): S131-S137, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38662696

Mass drug administration (MDA) of antifilarial drugs is the main strategy for the elimination of lymphatic filariasis (LF). Recent clinical trials indicated that the triple-drug therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) is much more effective against LF than the widely used two-drug combinations (albendazole plus either ivermectin or diethylcarbamazine). For IDA-based MDA, the stop-MDA decision is made based on microfilariae (mf) prevalence in adults. In this study, we assess how the probability of eventually reaching elimination of transmission depends on the critical threshold used in transmission assessment surveys (TAS-es) to define whether transmission was successfully suppressed and triple-drug MDA can be stopped. This analysis focuses on treatment-naive Indian settings. We do this for a range of epidemiological and programmatic contexts, using the established LYMFASIM model for transmission and control of LF. Based on our simulations, a single TAS, one year after the last MDA round, provides limited predictive value of having achieved suppressed transmission, while a higher MDA coverage increases elimination probability, thus leading to a higher predictive value. Every additional TAS, conditional on previous TAS-es being passed with the same threshold, further improves the predictive value for low values of stop-MDA thresholds. An mf prevalence threshold of 0.5% corresponding to TAS-3 results in ≥95% predictive value even when the MDA coverage is relatively low.


Albendazole , Diethylcarbamazine , Drug Therapy, Combination , Elephantiasis, Filarial , Filaricides , Ivermectin , Mass Drug Administration , Microfilariae , Elephantiasis, Filarial/drug therapy , Elephantiasis, Filarial/epidemiology , Elephantiasis, Filarial/prevention & control , Humans , Albendazole/therapeutic use , Albendazole/administration & dosage , Filaricides/therapeutic use , Diethylcarbamazine/therapeutic use , Diethylcarbamazine/administration & dosage , Ivermectin/therapeutic use , Ivermectin/administration & dosage , Animals , India/epidemiology , Microfilariae/drug effects , Adult , Prevalence
7.
Clin Infect Dis ; 78(Supplement_2): S93-S100, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38662701

BACKGROUND: Mass drug administration (MDA) is the cornerstone for the elimination of lymphatic filariasis (LF). The proportion of the population that is never treated (NT) is a crucial determinant of whether this goal is achieved within reasonable time frames. METHODS: Using 2 individual-based stochastic LF transmission models, we assess the maximum permissible level of NT for which the 1% microfilaremia (mf) prevalence threshold can be achieved (with 90% probability) within 10 years under different scenarios of annual MDA coverage, drug combination and transmission setting. RESULTS: For Anopheles-transmission settings, we find that treating 80% of the eligible population annually with ivermectin + albendazole (IA) can achieve the 1% mf prevalence threshold within 10 years of annual treatment when baseline mf prevalence is 10%, as long as NT <10%. Higher proportions of NT are acceptable when more efficacious treatment regimens are used. For Culex-transmission settings with a low (5%) baseline mf prevalence and diethylcarbamazine + albendazole (DA) or ivermectin + diethylcarbamazine + albendazole (IDA) treatment, elimination can be reached if treatment coverage among eligibles is 80% or higher. For 10% baseline mf prevalence, the target can be achieved when the annual coverage is 80% and NT ≤15%. Higher infection prevalence or levels of NT would make achieving the target more difficult. CONCLUSIONS: The proportion of people never treated in MDA programmes for LF can strongly influence the achievement of elimination and the impact of NT is greater in high transmission areas. This study provides a starting point for further development of criteria for the evaluation of NT.


Albendazole , Elephantiasis, Filarial , Filaricides , Ivermectin , Mass Drug Administration , Elephantiasis, Filarial/drug therapy , Elephantiasis, Filarial/prevention & control , Elephantiasis, Filarial/epidemiology , Elephantiasis, Filarial/transmission , Humans , Animals , Filaricides/therapeutic use , Filaricides/administration & dosage , Albendazole/administration & dosage , Albendazole/therapeutic use , Ivermectin/administration & dosage , Ivermectin/therapeutic use , Prevalence , Anopheles/parasitology , Disease Eradication/methods , Wuchereria bancrofti/drug effects , Diethylcarbamazine/administration & dosage , Diethylcarbamazine/therapeutic use , Drug Therapy, Combination
8.
Acta Parasitol ; 69(1): 929-950, 2024 Mar.
Article En | MEDLINE | ID: mdl-38489009

PURPOSE: Resistance and adverse consequences of albendazole (ABZ) in treating trichinellosis urged demand for secure and effective new drugs. The current study aimed to assess the effect of chitosan-coated lipid nano-combination with albendazole and miltefosine (MFS) in treating experimental murine trichinellosis and evaluating pathological and immunological changes of trichinellosis. MATERIALS AND METHODS: One hundred twenty Swiss albino mice were divided into six groups. Each group was subdivided into a and b subgroups based on the scarification time, which was 7- and 40-days post-infection (PI), respectively. The treatment efficacy was evaluated using parasitological, histopathological, serological (interleukin (IL)-12 and IL-4 serum levels), immunohistochemical (GATA3, glutathione peroxidase1 (GPX1) and caspase-3), and scanning electron microscopy (SEM) methods. RESULTS: The most effective drug was nanostructured lipid carriers (NLCs) loaded with ABZ (G5), which showed the most significant reduction in adults and larval count (100% and 92.39%, respectively). The greatest amelioration in histopathological changes was reported in G4 treated with MFS. GATA3 and caspase-3 were significantly reduced in all treated groups. GPX1 was significantly increased in G6 treated with MFS + NLCs. The highest degenerative effects on adults and larvae by SEM were documented in G6. CONCLUSION: Loading ABZ or MFS on chitosan-coated NLCs enhanced their efficacy against trichinellosis. Although ABZ was better than MFS, their combination should be considered as MFS caused a significant reduction in the intensity of infection. Furthermore, MFS showed anti-inflammatory (↓GATA3) and antiapoptotic effects (↓caspase-3), especially in the muscular phase. Also, when loaded with NLCS, it showed an antioxidant effect (↑GPX1).


Albendazole , Chitosan , Phosphorylcholine , Phosphorylcholine/analogs & derivatives , Trichinellosis , Animals , Mice , Chitosan/chemistry , Albendazole/administration & dosage , Albendazole/pharmacology , Trichinellosis/drug therapy , Phosphorylcholine/administration & dosage , Phosphorylcholine/pharmacology , Anthelmintics/administration & dosage , Lipids/blood , Drug Carriers/chemistry , Nanoparticles/chemistry , Immunohistochemistry , Male
9.
Acta Parasitol ; 69(1): 1090-1094, 2024 Mar.
Article En | MEDLINE | ID: mdl-38493433

BACKGROUND: Co-infection with other microorganisms such as parasites in patients with COVID-19 can affect the clinical outcome and require prompt diagnosis and appropriate therapy. CASE PRESENTATION: We present a case of an adult male with chest pain, dyspnea, cough, diplopia, and anorexia who was confirmed to have acute COVID-19 pneumonia. 2 weeks prior to admission, a hydatid lung cyst was identified on examination, but the patient refused surgery. Thoracoabdominal computed tomography (CT) revealed a rupture of the lung hydatid cyst and co-infection with COVID-19. The patient has prescribed a treatment protocol for COVID-19 and albendazole. Despite measures taken to manage severe inflammation and decreasing blood oxygen levels, the patient required admission to the intensive care unit (ICU) and intubation. After approximately 3 weeks of hospitalization, the patient was successfully extubated and discharged uneventfully from the hospital. Oral albendazole was prescribed for follow-up treatment. CONCLUSION: Our case highlights the importance of considering hydatid cysts in the differential diagnosis of patients with COVID-19, especially those living in endemic areas.


Albendazole , COVID-19 , Echinococcosis, Pulmonary , COVID-19/complications , COVID-19/diagnosis , Humans , Male , Echinococcosis, Pulmonary/complications , Echinococcosis, Pulmonary/diagnosis , Echinococcosis, Pulmonary/diagnostic imaging , Albendazole/therapeutic use , Albendazole/administration & dosage , Tomography, X-Ray Computed , SARS-CoV-2 , Coinfection/parasitology , Coinfection/diagnosis , Middle Aged , Lung/parasitology , Lung/diagnostic imaging , Lung/pathology , Severity of Illness Index
10.
Rev. esp. enferm. dig ; 115(12): 747-748, Dic. 2023. tab
Article En, Es | IBECS | ID: ibc-228737

Hydatidosis is a zoonosis caused by the larval stage of the genus Echinococcus. Humans are an accidental intermediate host. The main organ affected is the liver (70%). The incidence increases in endemic regions such as North Africa, Eastern Europe and South America. We present a descriptive series of cases treated in our hospital in the last 5 years. Demographic variables, cyst characteristics, as well as preoperative and postoperative variables are collected.(AU)


Humans , Animals , Male , Female , Middle Aged , Echinococcosis/surgery , Cysts , Albendazole/administration & dosage , Epidemiology, Descriptive , Retrospective Studies , Echinococcosis
12.
N Engl J Med ; 388(20): 1863-1875, 2023 May 18.
Article En | MEDLINE | ID: mdl-37195942

BACKGROUND: Current treatments for soil-transmitted helminth infections in humans have low efficacy against Trichuris trichiura. Emodepside - a drug in veterinary use and under development for the treatment of onchocerciasis in humans - is a leading therapeutic candidate for soil-transmitted helminth infection. METHODS: We conducted two phase 2a, dose-ranging, randomized, controlled trials to evaluate the efficacy and safety of emodepside against T. trichiura and hookworm infections. We randomly assigned, in equal numbers, adults 18 to 45 years of age in whom T. trichiura or hookworm eggs had been detected in stool samples to receive emodepside, at a single oral dose of 5, 10, 15, 20, 25, or 30 mg; albendazole, at a single oral dose of 400 mg; or placebo. The primary outcome was the percentage of participants who were cured of T. trichiura or hookworm infection (the cure rate) with emodepside 14 to 21 days after treatment, determined with the use of the Kato-Katz thick-smear technique. Safety was assessed 3, 24, and 48 hours after the receipt of treatment or placebo. RESULTS: A total of 266 persons were enrolled in the T. trichiura trial and 176 in the hookworm trial. The predicted cure rate against T. trichiura in the 5-mg emodepside group (85% [95% confidence interval {CI}, 69 to 93]; 25 of 30 participants) was higher than the predicted cure rate in the placebo group (10% [95% CI, 3 to 26]; 3 of 31 participants) and the observed cure rate in the albendazole group (17% [95% CI, 6 to 35]; 5 of 30 participants). A dose-dependent relationship was shown in participants with hookworm: the observed cure rate was 32% (95% CI, 13 to 57; 6 of 19 participants) in the 5-mg emodepside group and 95% (95% CI, 74 to 99.9; 18 of 19 participants) in the 30-mg emodepside group; the observed cure rates were 14% (95% CI, 3 to 36; 3 of 21 participants) in the placebo group and 70% (95% CI, 46 to 88; 14 of 20 participants) in the albendazole group. In the emodepside groups, headache, blurred vision, and dizziness were the most commonly reported adverse events 3 and 24 hours after treatment; the incidence of events generally increased in a dose-dependent fashion. Most adverse events were mild in severity and were self-limited; there were few moderate and no serious adverse events. CONCLUSIONS: Emodepside showed activity against T. trichiura and hookworm infections. (Funded by the European Research Council; ClinicalTrials.gov number, NCT05017194.).


Albendazole , Antinematodal Agents , Depsipeptides , Hookworm Infections , Trichuriasis , Adult , Animals , Humans , Albendazole/administration & dosage , Albendazole/adverse effects , Albendazole/therapeutic use , Feces/parasitology , Hookworm Infections/drug therapy , Soil/parasitology , Trichuriasis/drug therapy , Trichuris , Depsipeptides/administration & dosage , Depsipeptides/adverse effects , Depsipeptides/therapeutic use , Antinematodal Agents/administration & dosage , Antinematodal Agents/adverse effects , Antinematodal Agents/therapeutic use , Young Adult , Middle Aged , Administration, Oral , Dose-Response Relationship, Drug
13.
J Helminthol ; 97: e36, 2023 Apr 18.
Article En | MEDLINE | ID: mdl-37070392

Currently, no effective treatment is available for trichinellosis, a zoonotic parasitic disease caused by infection with the genus Trichinella. Kaempferol (KPF), a dietary flavonoid, has been documented to have anti-parasitic effects and various medicinal uses. Thus, this study aimed to investigate the efficacy of KPF in preventing and treating the intestinal and muscular phases of trichinellosis in mice compared with albendazole (ABZ). To achieve this, mice were divided into six groups: negative control; positive control; KPF prophylaxis; KPF treatment; ABZ treatment; and a combination of ABZ and KPF. Parasitological, histopathological and immunohistochemical evaluations were conducted to assess the effectiveness of the treatments. The parasitological assessment involved counting small intestinal adult worms and encysted muscle larvae. Additionally, the histopathological evaluation used the haematoxylin and eosin staining method for intestinal and muscular sections and picrosirius red stain for muscular sections. Moreover, the immunohistochemical expression of the intestinal NOD-like receptor-pyrin domain containing 3 (NLRP3) was evaluated. The group treated with combined drugs demonstrated a statistically significant reduction in the count of adults and encysted larvae (P < 0.05), a remarkable improvement in the inflammation of the intestines and muscles and a decrease in the thickness of the larvae's capsular layer. Additionally, the highest reduction in NLRP3 expression was observed in this group. Based on this study, KPF shows promise as an anti-trichinellosis medication that, when taken with ABZ, has a synergistic impact by modulating inflammation and larval capsule formation.


Intestinal Diseases, Parasitic , Kaempferols , Trichinella spiralis , Trichinellosis , Animals , Male , Mice , Albendazole/administration & dosage , Intestinal Diseases, Parasitic/drug therapy , Kaempferols/administration & dosage , Trichinella spiralis/physiology , Trichinellosis/drug therapy , Anthelmintics/administration & dosage
14.
PLoS Negl Trop Dis ; 16(2): e0010096, 2022 02.
Article En | MEDLINE | ID: mdl-35139070

BACKGROUND: Papua New Guinea (PNG) has a high burden of lymphatic filariasis (LF) caused by Wuchereria bancrofti, with an estimated 4.2 million people at risk of infection. A single co-administered dose of ivermectin, diethylcarbamazine and albendazole (IDA) has been shown to have superior efficacy in sustained clearance of microfilariae compared to diethylcarbamazine and albendazole (DA) in small clinical trials. A community-based cluster-randomised trial of DA versus IDA was conducted to compare the safety and efficacy of IDA and DA for LF in a moderately endemic, treatment-naive area in PNG. METHODOLOGY: All consenting, eligible residents of 24 villages in Bogia district, Madang Province, PNG were enrolled, screened for W. bancrofti antigenemia and microfilaria (Mf) and randomised to receive IDA (N = 2382) or DA (N = 2181) according to their village of residence. Adverse events (AE) were assessed by active follow-up for 2 days and passive follow-up for an additional 5 days. Antigen-positive participants were re-tested one year after MDA to assess treatment efficacy. PRINCIPAL FINDINGS: Of the 4,563 participants enrolled, 96% were assessed for AEs within 2 days after treatment. The overall frequency of AEs were similar after either DA (18%) or IDA (20%) treatment. For those individuals with AEs, 87% were mild (Grade 1), 13% were moderate (Grade 2) and there were no Grade 3, Grade 4, or serious AEs (SAEs). The frequency of AEs was greater in Mf-positive than Mf-negative individuals receiving IDA (39% vs 20% p<0.001) and in Mf-positive participants treated with IDA (39%), compared to those treated with DA (24%, p = 0.023). One year after treatment, 64% (645/1013) of participants who were antigen-positive at baseline were re-screened and 74% of these participants (475/645) remained antigen positive. Clearance of Mf was achieved in 96% (52/54) of infected individuals in the IDA arm versus 84% (56/67) of infected individuals in the DA arm (relative risk (RR) 1.15; 95% CI, 1.02 to 1.30; p = 0.019). Participants receiving DA treatment had a 4-fold higher likelihood of failing to clear Mf (RR 4.67 (95% CI: 1.05 to 20.67; p = 0.043). In the DA arm, a significant predictor of failure to clear was baseline Mf density (RR 1.54; 95% CI, 1.09 to 2.88; p = 0.007). CONCLUSION: IDA was well tolerated and more effective than DA for clearing Mf. Widespread use of this regimen could accelerate LF elimination in PNG. TRIAL REGISTRATION: Registration number NCT02899936; https://clinicaltrials.gov/ct2/show/NCT02899936.


Albendazole/administration & dosage , Diethylcarbamazine/administration & dosage , Elephantiasis, Filarial/drug therapy , Filaricides/administration & dosage , Ivermectin/administration & dosage , Adolescent , Adult , Aged , Albendazole/adverse effects , Animals , Child , Child, Preschool , Diethylcarbamazine/adverse effects , Drug Therapy, Combination , Elephantiasis, Filarial/parasitology , Female , Humans , Ivermectin/adverse effects , Male , Mass Drug Administration , Middle Aged , Papua New Guinea , Treatment Outcome , Wuchereria bancrofti/drug effects , Wuchereria bancrofti/physiology , Young Adult
15.
Int J Mol Sci ; 23(3)2022 Jan 24.
Article En | MEDLINE | ID: mdl-35163203

At present, the use of benzimidazole drugs in veterinary medicine is strongly limited by both pharmacokinetics and formulative issues. In this research, the possibility of applying an innovative semi-solid extrusion 3D printing process in a co-axial configuration was speculated, with the aim of producing a new gastro-retentive dosage form loaded with ricobendazole. To obtain the drug delivery system (DDS), the ionotropic gelation of alginate in combination with a divalent cation during the extrusion was exploited. Two feeds were optimized in accordance with the printing requirements and the drug chemical properties: the crosslinking ink, i.e., a water ethanol mixture containing CaCl2 at two different ratios 0.05 M and 0.1 M, hydroxyethyl cellulose 2% w/v, Tween 85 0.1% v/v and Ricobendazole 5% w/v; and alginate ink, i.e., a sodium alginate solution at 6% w/v. The characterization of the dried DDS obtained from the extrusion of gels containing different amounts of calcium chloride showed a limited effect on the ink extrudability of the crosslinking agent, which on the contrary strongly influenced the final properties of the DDS, with a difference in the polymeric matrix toughness and resulting effects on floating time and drug release.


Albendazole/analogs & derivatives , Drug Delivery Systems/methods , Albendazole/administration & dosage , Albendazole/pharmacology , Alginates/chemistry , Calcium Chloride/chemistry , Drug Compounding/methods , Drug Delivery Systems/instrumentation , Drug Delivery Systems/veterinary , Drug Liberation , Gels/chemistry , Hexuronic Acids/chemistry , Printing, Three-Dimensional
16.
Molecules ; 27(3)2022 Jan 24.
Article En | MEDLINE | ID: mdl-35164028

Combination therapy of many anthelmintic drugs has been used to achieve fast animal curing. Q-DRENCH is an oral suspension, containing four different active drugs against GIT worms in sheep, commonly used in Australia and New Zeeland. The anti-parasitic drugs are Albendazole (ALB), Levamisole HCl (LEV), Abamectin (ABA), and Closantel (CLO). The main purpose of this study is to present a new simultaneous stability-indicting HPLC-DAD method for the analysis of the four drugs. The recommended liquid system was 1 mL of Triethylamine/L water, adjusting the pH to 3.5 by glacial acetic acid: acetonitrile solvent (20:80, v/v). Isocratic elusion achieved the desired results of separation at a 2 mL/min flow rate using Zorbax C-18 as a stationary phase. Detection was performed at 210 nm. The linearity ranges were 15.15 to 93.75 µg/mL for ALB, 25 to 150 µg/mL for LEV, 30 to 150 µg/mL for ABA, and 11.7 to 140.63 µg/mL for CLO. Moreover, the final greenness score was 0.62 using the AGREE tool, which reflects the eco-friendly nature. Moreover, the four drugs were determined successfully in the presence of their stressful degradation products. This work presents the first chromatographic method for simultaneous analysis for Q-DRENCH oral suspension drugs in the presence of their stressful degradation products.


Albendazole/analysis , Ivermectin/analogs & derivatives , Levamisole/analysis , Salicylanilides/analysis , Administration, Oral , Albendazole/administration & dosage , Albendazole/chemistry , Albendazole/pharmacokinetics , Animals , Anthelmintics/administration & dosage , Anthelmintics/analysis , Anthelmintics/chemistry , Anthelmintics/pharmacokinetics , Australia , Chromatography, High Pressure Liquid/methods , Drug Stability , Evaluation Studies as Topic , Ivermectin/administration & dosage , Ivermectin/analysis , Ivermectin/chemistry , Ivermectin/pharmacokinetics , Levamisole/administration & dosage , Levamisole/chemistry , Levamisole/pharmacokinetics , Limit of Detection , New Zealand , Salicylanilides/administration & dosage , Salicylanilides/chemistry , Salicylanilides/pharmacokinetics , Sheep , Suspensions
17.
Trop Med Int Health ; 27(1): 81-91, 2022 01.
Article En | MEDLINE | ID: mdl-34704320

OBJECTIVES: Targeted deworming is the current strategy for control of morbidity associated with soil-transmitted helminths (STH) among at-risk populations: preschool-aged children, school-aged children and women of childbearing age. We report the prevalence and intensity of STH in a district after lymphatic filariasis (LF) mass drug administration (MDA) in southern India where albendazole was co-administered from 2001. METHODS: Children aged 2 to 15 years and adults (defined as ≥15 years) in a rural administrative block of Tamil Nadu were recruited using a probability proportional to size method. Stool samples were screened and eggs per gram (EPG) determined by Kato-Katz method. Multilevel logistic regression (MLR) and multilevel negative binomial regression (MNBR) analyses were used to identify factors associated with infection and intensity, respectively. RESULTS: Of 862 participants who provided samples, 60 (7.0%; 95% confidence interval (CI): 5.3-8.7) were positive for STH with a predominance of hookworm infections (n = 57, 6.6%; 95% CI: 5.0-8.3). Increasing age (odds ratio (OR): 1.09; 95% CI: 1.04-1.15) and regular usage of the toilet (OR: 0.32; 95% CI: 0.12-0.88) were independently associated with hookworm infection and age was significantly associated with increasing intensity of hookworm infection (infection intensity ratio (IIR): 1.28; 95% CI: 1.19-1.37). A brief review of STH prevalence in endemic settings before and after the stoppage of LF MDA indicated that, in most settings, a substantial reduction in STH prevalence is seen. CONCLUSION: Community-wide MDA in all age groups in these post-LF MDA districts with low prevalence and light intensity infections could result in transmission interruption of STH.


Albendazole/therapeutic use , Anthelmintics/therapeutic use , Elephantiasis, Filarial/epidemiology , Soil Microbiology , Adolescent , Adult , Aged , Albendazole/administration & dosage , Animals , Anthelmintics/administration & dosage , Child , Child, Preschool , Cross-Sectional Studies , Elephantiasis, Filarial/drug therapy , Elephantiasis, Filarial/parasitology , Feces/parasitology , Female , Humans , India/epidemiology , Infant , Male , Middle Aged , Prevalence , Rural Health Services , Surveys and Questionnaires , Young Adult
18.
Anticancer Drugs ; 33(1): 19-29, 2022 01 01.
Article En | MEDLINE | ID: mdl-34261920

Albendazole (ABZ), a clinical antiparasitic drug, has shown potential antitumor effects in various tumors. Herein, we prepared dimeric cRGD [(cRGD)2] modified human serum albumin (HSA) nanosystem to co-delivery of albendazole (ABZ) and iodine-131 (131I) for chemoradiotherapy of triple-negative breast cancer (TNBC). HSA@ABZ NPs were synthesized by the self-assembly method. 131I-(cRGD)2/HSA@ABZ NPs were fabricated through covalently binding HSA@ABZ NPs with (cRGD)2 peptides, followed by chloramine T direct labeling with 131I. In vitro therapeutic effects on TNBC (MDA-MB-231 and 4T1 cells) were determined using MTT assay, crystal violet assay, wound-healing assay and western blotting analysis. In vivo treatment was performed using 4T1-bearing mice, and the tumor-targeting efficacy was assessed by gamma imaging. The distribution of NPs was quantitatively analyzed by detecting the gamma counts in tumor and main organs. The nanoparticles possessed negative charge, moderate size and good polydispersity index. Dual responding to pH and redox, the in vitro release rate of ABZ was more than 80% in 72 h. In vitro, NPs inhibited the proliferation of TNBC cells in a concentration-dependent manner and decreased cell migration. Western blotting analysis showed that the NPs, as well as free ABZ, cell-dependently induced autophagy and apoptosis by restraining or promoting the expression of p-p38 and p-JNK MAPK. In vivo, gamma imaging exhibited an earlier and denser radioactivity accumulation in tumor of 131I-(cRGD)2/HSA@ABZ NPs compared to NPs free of (cRGD)2 conjugating. Furthermore, 131I-(cRGD)2/HSA@ABZ NPs significantly suppressed tumor growth by restraining proliferation and promoting apoptosis in vivo. Our study suggested that the nanoparticles we developed enhanced tumor-targeting of ABZ and increased antitumor effects by combination of chemotherapy and radiotherapy.


Albendazole/pharmacology , Chemoradiotherapy/methods , Iodine Radioisotopes/pharmacology , Nanoparticles/chemistry , Peptides, Cyclic/chemistry , Triple Negative Breast Neoplasms/pathology , Albendazole/administration & dosage , Animals , Apoptosis/drug effects , Autophagy/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Dose-Response Relationship, Drug , Drug Carriers/chemistry , Drug Liberation , Drug Stability , Humans , Hydrogen-Ion Concentration , Iodine Radioisotopes/administration & dosage , Mice, Inbred BALB C , Particle Size , Serum Albumin , Surface Properties , Temperature , Xenograft Model Antitumor Assays
19.
PLoS One ; 16(12): e0260722, 2021.
Article En | MEDLINE | ID: mdl-34932602

INTRODUCTION: The Geshiyaro project aims to break transmission of soil-transmitted helminths and schistosomiasis in the Wolaita Zone of Ethiopia through a combination of two interventions: behavior change communication (BCC) for increased water, sanitation and hygiene (WaSH) infrastructure use alongside preventive chemotherapy (PC) using albendazole (ALB) and praziquantel (PZQ), targeted to reach 90% treatment coverage. Coverage evaluation surveys (CES) were conducted post-treatment, and the resultant survey coverage was compared to reported administrative coverage. This provided a secondary confirmation of the Geshiyaro project coverages, and is used to monitor the success of each Mass Drug Administration (MDA) round. METHODS: A community-based cross-sectional study was conducted in 13 woredas (districts) of the Wolaita Zone. All eligible individuals from the selected households were invited for an interview. The study design, sample size, analysis and report writing were conducted according to the World Health Organization (WHO) CES guidelines for PC. RESULTS: The study interviewed a total of 3,568 households and 18,875 individuals across 13 woredas in the Wolaita Zone. Overall, the survey coverage across all studied woredas was 81.5% (95% CI; 80.9-82.0%) for both ALB and PZQ. Reported administrative coverage across all studied woredas was higher than survey coverage, 92.7% and 91.2% for ALB and PZQ, respectively. A significant portion of individuals (17.6%) were not offered PC. The predominant reason for not achieving the target coverage of 90% was beneficiary absenteeism during MDA (6.6% ALB, 6.8% PZQ), followed by drug distributors failing to reach all households (4.7% ALB, 4.8% PZQ), and beneficiaries not informed of the program (1.3% ALB, 1.7% PZQ). CONCLUSION: Programmatic actions will need to be taken during the next MDA campaign to achieve the targeted Geshiyaro project coverage threshold across data collection and program engagement. Adequate training and supervision on recording and reporting administrative coverage should be provided, alongside improved social mobilization of treated communities to increase participation, and strengthened institutional partnerships and communication.


Albendazole/administration & dosage , Anthelmintics/administration & dosage , Chemoprevention/methods , Helminthiasis/prevention & control , Praziquantel/administration & dosage , Schistosomiasis/prevention & control , Adolescent , Adult , Animals , Child , Child, Preschool , Cross-Sectional Studies , Ethiopia/epidemiology , Family Characteristics , Female , Helminthiasis/epidemiology , Helminthiasis/parasitology , Helminthiasis/transmission , Humans , Hygiene/education , Infant , Male , Mass Drug Administration/statistics & numerical data , Middle Aged , Prevalence , Sanitation/methods , Schistosomiasis/epidemiology , Schistosomiasis/parasitology , Schistosomiasis/transmission , Soil/parasitology , Surveys and Questionnaires
20.
S Afr Med J ; 111(11): 1050-1054, 2021 11 05.
Article En | MEDLINE | ID: mdl-34949267

A previously healthy 10-year-old girl, living in a sheep-farming community in South Africa with exposure to dogs, presented to her local hospital with generalised tonic-clonic seizures. The initial clinical assessment and laboratory work-up were unremarkable. When she presented with further seizures 6 months later, attempts to arrange neuroimaging and specialist assessment were unsuccessful owing to restrictions on routine healthcare services during the SARS-CoV-2 nationwide lockdown. Subsequently, 11 months after her first presentation, she developed focal neurological signs suggestive of raised intracranial pressure. A brain computed tomography scan revealed a left-sided cerebral cyst and imminent tonsillar herniation. An emergency burr-hole procedure was performed to relieve the raised intracranial pressure, followed by definitive neurosurgical excision of cysts. Hydatid protoscolices and hooklets were seen on microscopy of cyst fluid, and treatment with albendazole and praziquantel was initiated. While her infection was treated successfully, long-term sequelae including permanent blindness and hemiparesis could potentially have been prevented with early neuroimaging and surgical intervention.


Anticestodal Agents/administration & dosage , Brain Diseases/diagnosis , COVID-19 , Echinococcosis/diagnosis , Albendazole/administration & dosage , Brain Diseases/drug therapy , Brain Diseases/parasitology , Child , Delayed Diagnosis , Echinococcosis/drug therapy , Female , Humans , Intracranial Hypertension/parasitology , Praziquantel/administration & dosage , Seizures/parasitology , South Africa , Tomography, X-Ray Computed
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