-
BMC Complementary Medicine and Therapies Jan 2023Trichinellosis, a zoonosis caused by the genus Trichinella, is a widespread foodborne disease. Albendazole, one of the benzimidazole derivatives, is used for treating...
BACKGROUND
Trichinellosis, a zoonosis caused by the genus Trichinella, is a widespread foodborne disease. Albendazole, one of the benzimidazole derivatives, is used for treating human trichinellosis, but with limited efficacy in killing the encysted larvae and numerous adverse effects. Cyperus rotundus L. is a herbal plant with a wide range of medicinal uses, including antiparasitic, and is frequently used in traditional medicine to treat various illnesses.
METHODS
LC-ESI-MS was used to identify the active phytoconstituents in the methanol extract (MeOH ext.) of the aerial parts of C. rotundus and its derivate fractions ethyl acetate (EtOAc fr.), petroleum ether (pet-ether fr.), and normal butanol (n-BuOH fr.). The in vivo therapeutic effects of C. rotundus fractions of the extracts were evaluated using the fraction that showed the most promising effect after detecting their in vitro anti-Trichinella spiralis potential.
RESULTS
C. rotundus extracts are rich in different phytochemicals, and the LC-ESI-MS of the 90% methanol extract identified 26 phenolic compounds classified as phenolic acids, flavonoids, and organic acids. The in vitro studies showed that C. rotundus extracts had a lethal effect on T. spiralis adults, and the LC were 156.12 µg/ml, 294.67 µg/ml, 82.09 µg/ml, and 73.16 µg/ml in 90% MeOH ext., EtOAc fr., pet-ether fr. and n-BuOH fr., respectively. The n-BuOH fr. was shown to have the most promising effects in the in vitro studies, which was confirmed by scanning electron microscopy. The in vivo effects of n-BuOH fr. alone and in combination with albendazole using a mouse model were evaluated by counting adults in the small intestine and larvae in the muscles, in addition to the histopathological changes in the small intestine and the muscles. In the treated groups, there was a significant decrease in the number of adults and larvae compared to the control group. Histopathologically, treated groups showed a remarkable improvement in the small intestine and muscle changes. Remarkably, maximal therapeutic effects were detected in the combination therapy compared to each monotherapy.
CONCLUSION
Accordingly, C. rotundus extracts may have anti-T. spiralis potential, particularly when combined with albendazole, and they may be used as synergistic to anti-T. spiralis medication therapy.
Topics: Humans; Albendazole; Plant Extracts; Cyperus; Methanol; Anthelmintics; Ethers
PubMed: 36658562
DOI: 10.1186/s12906-023-03839-7 -
Biomedicine & Pharmacotherapy =... Apr 2021Surgery remains the preferred treatment option for hydatid cyst (cystic echinococcosis); however, recent studies have demonstrated that the current protoscolicidal...
BACKGROUND
Surgery remains the preferred treatment option for hydatid cyst (cystic echinococcosis); however, recent studies have demonstrated that the current protoscolicidal agents used during surgery are associated with some adverse side effects such as biliary fibrosis, hepatic necrosis, and cirrhosis. The present study aims to evaluate the in vitro and ex vivo anti-parasitic effects of copper nanoparticles (CuNPs) alone and combined with albendazole on hydatid cyst protoscoleces.
METHODS
CuNPs was green synthesized using C. spinosa extract. Various concentrations of CuNPs (250, 500, and 750 mg/mL) alone and combined with albendazole (ALZ, 200 mg/mL) were exposed to protoscoleces collected from the liver fertile hydatid cysts of infected sheep for 5-60 min in vitro and ex vivo. Next, the eosin exclusion test was applied to determine the viability of protoscoleces. Caspase-3 like activity of CuNPs-treated protoscoleces was then evaluated using the colorimetric protease assay Sigma Kit based on the manufacturer's instructions.
RESULTS
Scanning electron microscopy (SEM) results showed that the particle size of CuNPs was 17 and 41 nm with the maximum peak at the wavelength of 414 nm. The maximum protoscolicidal activity of CuNPs was observed at the concentration of 750 mg/mL in vitro, so that 73.3 % of protoscoleces were killed after 60 min of exposure. Meanwhile, the mortality of protoscoleces was 100 % after 10 min of exposure to 750 mg/mL of CuNPs along with ALZ (200 mg/mL). Nevertheless, the findings proved that CuNPs even in combination with ALZ required a longer time to kill protoscoleces ex vivo. After 48 h of treating protoscoleces, CuNPs in a dose-dependent manner and at doses of 250, 500, and 750 mg/mL induced the caspase enzyme activation by 20.5 %, 32.3 %, and 36.1 %, respectively.
CONCLUSION
The findings of the present investigation showed potent protoscolicidal effects of CuNPs, especially combined with albendazole, which entirely eliminated the parasite after 10-20 min of exposure. The results also showed that although the possible protoscolicidal mechanisms of CuNPs are not clearly understood, the inducing apoptosis through caspases is one of the main protoscolicidal mechanisms of CuNPs. However, supplementary studies, especially in animal models and clinical settings, are needed to approve these results.
Topics: Albendazole; Animals; Anticestodal Agents; Apoptosis; Caspase 3; Copper; Drug Compounding; Echinococcosis, Hepatic; Echinococcus granulosus; Metal Nanoparticles; Nanotechnology; Protozoan Proteins; Sheep, Domestic
PubMed: 33450495
DOI: 10.1016/j.biopha.2021.111257 -
Genetics Jul 2022Parasitic nematodes are major human and agricultural pests, and benzimidazoles are amongst the most important broad-spectrum anthelmintic drug class used for their...
Parasitic nematodes are major human and agricultural pests, and benzimidazoles are amongst the most important broad-spectrum anthelmintic drug class used for their control. Benzimidazole resistance is now widespread in many species of parasitic nematodes in livestock globally and an emerging concern for the sustainable control of human soil-transmitted helminths. β-tubulin is the major benzimidazole target, although other genes may influence resistance. Among the 6 Caenorhabditis elegans β-tubulin genes, loss of ben-1 causes resistance without other apparent defects. Here, we explored the genetics of C. elegans β-tubulin genes in relation to the response to the benzimidazole derivative albendazole. The most highly expressed β-tubulin isotypes, encoded by tbb-1 and tbb-2, were known to be redundant with each other for viability, and their products are predicted not to bind benzimidazoles. We found that tbb-2 mutants, and to a lesser extent tbb-1 mutants, were hypersensitive to albendazole. The double mutant tbb-2 ben-1 is uncoordinated and short, resembling the wild type exposed to albendazole, but the tbb-1 ben-1 double mutant did not show the same phenotypes. These results suggest that tbb-2 is a modifier of albendazole sensitivity. To better understand how BEN-1 mutates to cause benzimidazole resistance, we isolated mutants resistant to albendazole and found that 15 of 16 mutations occurred in the ben-1 coding region. Mutations ranged from likely nulls to hypomorphs, and several corresponded to residues that cause resistance in other organisms. Null alleles of ben-1 are albendazole-resistant and BEN-1 shows high sequence identity with tubulins from other organisms, suggesting that many amino acid changes could cause resistance. However, our results suggest that missense mutations conferring resistance are not evenly distributed across all possible conserved sites. Independent of their roles in benzimidazole resistance, tbb-1 and tbb-2 may have specialized functions as null mutants of tbb-1 or tbb-2 were cold or heat sensitive, respectively.
Topics: Albendazole; Animals; Anthelmintics; Benzimidazoles; Caenorhabditis elegans; Drug Resistance; Humans; Microtubules; Tubulin; Tubulin Modulators
PubMed: 35731216
DOI: 10.1093/genetics/iyac093 -
Infectious Diseases of Poverty Jun 2024Preventive chemotherapy with ivermectin and albendazole (IA) in mass drug administration (MDA) programs for all at-risk populations is the core public health...
Efficacy of ivermectin and albendazole combination in suppressing transmission of lymphatic filariasis following mass administration in Tanzania: a prospective cohort study.
BACKGROUND
Preventive chemotherapy with ivermectin and albendazole (IA) in mass drug administration (MDA) programs for all at-risk populations is the core public health intervention to eliminate lymphatic filariasis (LF). Achieving this goal depends on drug effectiveness in reducing parasite reservoirs in the community to halt transmission. We assessed the efficacy of ivermectin and albendazole in clearing microfilariae and circulating filarial antigens (CFA) following MDA.
METHODS
This community-based prospective study was conducted in Mkinga district, Tanga region, Tanzania, from November 2018 to June 2019. A total of 4115 MDA-eligible individuals were screened for CFA using Filarial test strips. CFA positives were re-examined for microfilariae by microscopy. CFA and microfilariae positive individuals were enrolled and received IA through MDA campaign. The status of microfilariae and CFA was monitored before MDA, and on day 7 and six-month following MDA. The primary efficacy outcomes were the clearance rates of microfilariae on day 7 and six-months, and CFA at 6 months of post-MDA. The McNemar test assessed the proportions of microfilariae positive pre- and post-MDA, while Chi-square tests were utilized to examine factors associated with CFA status six months post-MDA.
RESULTS
Out of 4115 individuals screened, 239 (5.8%) tested positive for CFA, of whom 11 (4.6%) were also positive for microfilariae. Out of the ten microfilariae-positive individuals available for follow-up on day 7, nine tested negative, yielding a microfilariae clearance rate of 90% [95% confidence interval (CI): 59.6-98.2%]. Participants who tested negative for microfilariae on day 7 remained free of microfilariae six months after MDA. However, those who did not clear microfilariae on day-7 remained positive six-months post-MDA. The McNemar test revealed a significant improvement in microfilariae clearance on day 7 following MDA (P = 0.02). Out of 183 CFA-positive individuals who were available at 6-month follow-up, 160 (87.4%) remained CFA positive, while 23 became CFA negative. The CFA clearance rate at 6 months post-MDA was 12.6% (95% CI: 8.5-8.5%). There was no significant association of variability in ivermectin plasma exposure, measured by maximum concentration or area under the curve, and the clearance status of microfilariae or CFA post-MDA.
CONCLUSIONS
Preventive chemotherapy with IA effectively clears microfilariae within a week. However, it is less effective in clearing CFA at six months of post-MDA. The low clearance rate for filarial antigenemia underscores the need for alternative drug combinations and additional preventive measures to achieve LF elimination by 2030.
Topics: Ivermectin; Albendazole; Tanzania; Humans; Elephantiasis, Filarial; Prospective Studies; Male; Mass Drug Administration; Female; Adult; Middle Aged; Adolescent; Young Adult; Animals; Child; Filaricides; Drug Therapy, Combination; Microfilariae; Aged; Child, Preschool; Antigens, Helminth; Treatment Outcome
PubMed: 38867265
DOI: 10.1186/s40249-024-01214-3 -
PLoS Neglected Tropical Diseases Oct 2023Several neglected tropical diseases (NTDs) employ mass drug administration (MDA) as part of their control or elimination strategies. This has historically required...
Perceptions and acceptability of co-administered albendazole, ivermectin and azithromycin mass drug administration, among the health workforce and recipient communities in Ethiopia.
Several neglected tropical diseases (NTDs) employ mass drug administration (MDA) as part of their control or elimination strategies. This has historically required multiple distinct campaigns, each targeting one or more NTDs, representing a strain on both the recipient communities and the local health workforce implementing the distribution. We explored perceptions and attitudes surrounding combined MDA among these two groups of stakeholders. Our qualitative study was nested within a cluster randomized non-inferiority safety trial of combined ivermectin, albendazole and azithromycin MDA. Using semi-structured question guides, we conducted 16 key informant interviews with selected individuals involved in implementing MDA within the participating district. To better understand the perceptions of recipient communities, we also conducted four focus group discussions with key community groups. Individuals were selected from both the trial arm (integrated MDA) and the control arm (standard MDA) to provide a means of comparison and discussion. All interviews and focus group discussions were led by fluent Afaan oromo speakers. Interviewers transcribed and later translated all discussions into English. The study team synthesized and analyzed the results via a coding framework and software. Most respondents appreciated the time and effort saved via the co-administered MDA strategy but there were some misgivings amongst community beneficiaries surrounding pill burden. Both the implementing health work force members and beneficiaries reported refusals stemming from lack of understanding around the need for the new drug regimen as well as some mistrust of government officials among the youth. The house-to-house distribution method, adopted as a COVID-19 prevention strategy, was by far preferred by all beneficiaries over central-point MDA, and may have led to greater acceptability of co-administration. Our data demonstrate that a co-administration strategy for NTDs is acceptable to both communities and health staff.
Topics: Adolescent; Humans; Ivermectin; Mass Drug Administration; Albendazole; Azithromycin; Ethiopia; Health Workforce; COVID-19; COVID-19 Drug Treatment
PubMed: 37782675
DOI: 10.1371/journal.pntd.0011332 -
PLoS Neglected Tropical Diseases Oct 2022Albendazole is an orally administered anti-parasitic medication with widespread usage in a variety of both programmatic and clinical contexts. Previous work has shown...
BACKGROUND
Albendazole is an orally administered anti-parasitic medication with widespread usage in a variety of both programmatic and clinical contexts. Previous work has shown that the drug's pharmacologically active metabolite, albendazole sulfoxide, is characterised by substantial inter-individual pharmacokinetic variation. This variation might have implications for the efficacy of albendazole treatment, but current understanding of the factors associated with this variation remains incomplete.
METHODOLOGY/PRINCIPAL FINDINGS
We carried out a systematic review to identify references containing temporally disaggregated data on the plasma concentration of albendazole and/or (its pharmacologically-active metabolite) albendazole sulfoxide following a single oral dose. These data were then integrated into a mathematical modelling framework to infer albendazole sulfoxide pharmacokinetic parameters and relate them to characteristics of the groups being treated. These characteristics included age, weight, sex, dosage, infection status, and whether patients had received a fatty meal prior to treatment or other drugs alongside albendazole. Our results highlight a number of factors systematically associated with albendazole sulfoxide pharmacokinetic variation including age, existing parasitic infection and receipt of a fatty meal. Age was significantly associated with variation in albendazole sulfoxide systemic availability and peak plasma concentration achieved; as well as the clearance rate (related to the half-life) after adjusting for variation in dosage due to differences in body weight between children and adults. Receipt of a fatty meal prior to treatment was associated with increased albendazole sulfoxide systemic availability (and by extension, peak plasma concentration and total albendazole sulfoxide exposure following the dose). Parasitic infection (particularly echinococcosis) was associated with altered pharmacokinetic parameters, with infected populations displaying distinct characteristics to uninfected ones.
CONCLUSIONS/SIGNIFICANCE
These results highlight the extensive inter-individual variation that characterises albendazole sulfoxide pharmacokinetics and provide insight into some of the factors associated with this variation.
Topics: Humans; Adult; Child; Albendazole; Anthelmintics; Echinococcosis; Administration, Oral
PubMed: 36306320
DOI: 10.1371/journal.pntd.0010497 -
International Health Dec 2020The development of the World Health Organization's Global Programme to Eliminate Lymphatic Filariasis (GPELF) can be interpreted through many different lenses-e.g. one... (Review)
Review
The development of the World Health Organization's Global Programme to Eliminate Lymphatic Filariasis (GPELF) can be interpreted through many different lenses-e.g. one focusing on the health or economic plight of affected individuals and populations, another tracking the individuals and organizations responsible for building the programme or, as in this review, one identifying each of the critical requirements and specific hurdles that need to be addressed in order to successfully construct the programme. For almost 75 y after the life cycle of LF was first described, the principal tool for countering it was vector control. Discovery that diethylcarbamazine (and later ivermectin and albendazole) could effectively treat affected and at-risk populations, along with the availability of a simple, field-based diagnostic test to monitor programme progress, provided the essential tools for LF elimination. Recognition of this potential by the global health community (including the World Health Assembly) led two pharmaceutical companies (GlaxoSmithKline and Merck) to make enormous, unprecedented donations of albendazole and ivermectin to achieve this goal. Additional resource support from the public and private sectors and from health ministries in the 80 LF-endemic countries led to the creation of a Global Alliance to Eliminate LF, which launched the GPELF in 2000, just 125 y after the LF life cycle was first described.
Topics: Albendazole; Diethylcarbamazine; Elephantiasis, Filarial; Filaricides; Humans; Ivermectin
PubMed: 33349877
DOI: 10.1093/inthealth/ihaa061 -
BMJ Case Reports Oct 2015
Topics: Adult; Albendazole; Anthelmintics; Breast; Cysticercosis; Female; Humans; India; Ultrasonography, Mammary
PubMed: 26491000
DOI: 10.1136/bcr-2015-211336 -
Indian Pediatrics Jan 2015
Topics: Albendazole; Anticestodal Agents; Child; Echinococcosis; Female; Hepatitis, Autoimmune; Humans; Transaminases
PubMed: 25638200
DOI: No ID Found -
Journal of Veterinary Diagnostic... Nov 2022Albendazole is a widely used anthelmintic drug that is labeled for the treatment of specific nematodes and flukes in ruminants. Albendazole is approved for the treatment...
Albendazole is a widely used anthelmintic drug that is labeled for the treatment of specific nematodes and flukes in ruminants. Albendazole is approved for the treatment of liver flukes in goats (10 mg/kg PO for a single dose), but is commonly used extra-label in situations in which parasite resistance is an issue. Albendazole toxicosis has been reported in pigeons, doves, alpacas, humans, dogs, and cats. Here we report an adverse event in a 6-mo-old goat associated with extra-label use of albendazole (35.7 mg/kg PO daily for 3 d). Clinicopathologic findings included severe diarrhea and death, with small intestinal crypt necrosis and dysplasia, and severe bone marrow hypoplasia. Microbial and molecular testing and transmission electron microscopy ruled out infectious organisms. The described pathologic changes are similar to those reported in other species that have experienced toxicosis associated with albendazole. To our knowledge, bone marrow and intestinal lesions associated with albendazole use in the goat have not been reported previously. Veterinarians should be aware of potential adverse events and toxicoses associated with anthelmintic drugs, especially as parasite resistance increases, and extra-label usage, and the use of such drugs without veterinary supervision, becomes more common.
Topics: Animals; Dogs; Humans; Albendazole; Goats; Parasite Egg Count; Bone Marrow; Goat Diseases; Ivermectin; Feces; Anthelmintics; Ruminants; Dog Diseases
PubMed: 36039773
DOI: 10.1177/10406387221121122