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International Journal For Parasitology.... Apr 2022Parasitic diseases are major constraints in fish mariculture. The anthelmintic praziquantel (PZQ) can effectively treat a range of flatworm parasites in a variety of... (Review)
Review
Parasitic diseases are major constraints in fish mariculture. The anthelmintic praziquantel (PZQ) can effectively treat a range of flatworm parasites in a variety of fish species and has potential for broader application than its current use in the global aquaculture industry. In this review we report on PZQ's current use in the aquaculture industry and discuss its efficacy against various flatworm parasites of fish. Routes of PZQ administration are evaluated, along with issues related to palatability, pharmacokinetics and toxicity in fish, while PZQ's effects on non-target species, environmental impacts, and the development of drug-resistance are discussed.
Topics: Animals; Anthelmintics; Aquaculture; Platyhelminths; Praziquantel
PubMed: 35220160
DOI: 10.1016/j.ijpddr.2022.02.001 -
The Cochrane Database of Systematic... Apr 2020Ascaris lumbricoides is a common infection, and mainly affects children living in low-income areas. Water and sanitation improvement, health education, and drug... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ascaris lumbricoides is a common infection, and mainly affects children living in low-income areas. Water and sanitation improvement, health education, and drug treatment may help break the cycle of transmission, and effective drugs will reduce morbidity.
OBJECTIVES
To compare the efficacy and safety of anthelmintic drugs (albendazole, mebendazole, ivermectin) for treating people with Ascaris infection.
SEARCH METHODS
We searched the Cochrane Infectious Disease Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, three other databases, and reference lists of included studies, without language restrictions, up to 4 July 2019.
SELECTION CRITERIA
Randomized controlled trials (RCT) that compared albendazole, mebendazole, and ivermectin in children and adults with confirmed Ascaris infection.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, assessed risk of bias, and extracted data from the included trials. A third review author checked the quality of data extraction. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) to compare dichotomous outcomes in treatment and control groups. We used the fixed-effect model for studies with low heterogeneity and the random-effects model for studies with moderate to high heterogeneity. We assessed the certainty of the evidence using the GRADE approach. We used the control rate average to provide illustrative cure rates in the comparison groups.
MAIN RESULTS
We included 30 parallel-group RCTs, which enrolled 6442 participants from 17 countries across Africa, Asia, Central America and the Caribbean, and South America. Participants were from 28 days to 82 years of age, recruited from school, communities, and health facilities. Twenty studies were funded or co-funded by manufacturers, while 10 studies were independent of manufacturer funding. Twenty-two trials had a high risk of bias for one or two domains (blinding, incomplete outcome data, selective reporting). Single dose of albendazole (four trials), mebendazole (three trials) or ivermectin (one trial) was compared to placebo. Parasitological cure at 14 to 60 days was high in all the studies (illustrative cure of 93.0% in the anthelmintic group and 16.1% in the placebo group; RR 6.29, 95% CI 3.91 to 10.12; 8 trials, 1578 participants; moderate-certainty evidence). Single dose of albendazole is as effective as multiple doses of albendazole (illustrative cure of 93.2% with single dose, 94.3% with multiple doses; RR 0.98, 95% CI 0.92 to 1.05; 3 trials, 307 participants; high-certainty evidence); or as single dose of mebendazole (illustrative cure of 98.0% with albendazole, 96.9% with mebendazole; RR 1.01, 95% CI 1.00 to 1.02; 6 trials, 2131 participants; high-certainty evidence). Studies did not detect a difference between a single dose of albendazole and a single dose of ivermectin (cure rates of 87.8% with albendazole, 90.2% with ivermectin; RR 0.99, 95% CI 0.91 to 1.08; 3 trials, 519 participants; moderate-certainty evidence). Across all the studies, failure after single dose of albendazole ranged from 0.0% to 30.3%, mebendazole from 0.0% to 22.2%, and ivermectin from 0.0% to 21.6%. The egg reduction rate (ERR) measured up to 60 days after the treatment was high in all treated groups, regardless of the anthelmintic used (range 96% to 100%). It was not possible to evaluate parasitological cure by classes of infection intensity. No included trials reported complication or serious adverse events. Other adverse events were apparently similar among the compared anthelmintic groups (moderate- to low-certainty evidence). The most commonly reported other adverse events were nausea, vomiting, abdominal pain, diarrhoea, headache, and fever.
AUTHORS' CONCLUSIONS
Single-dose of albendazole, mebendazole, and ivermectin all appeared effective against Ascaris lumbricoides infection, yielding high parasitological cure and large reductions in eggs excreted, with no differences detected between them. The drugs appear to be safe to treat children and adults with confirmed Ascaris infection. There is little to choose between drugs and regimens in terms of cure or adverse events.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albendazole; Animals; Anthelmintics; Ascariasis; Ascaris lumbricoides; Child; Child, Preschool; Humans; Infant; Ivermectin; Mebendazole; Middle Aged; Parasite Egg Count; Placebos; Randomized Controlled Trials as Topic; Young Adult
PubMed: 32289194
DOI: 10.1002/14651858.CD010599.pub2 -
Trends in Parasitology Nov 2014Anthelmintic drug efficacy (ADE) is generally estimated as a population average effect, despite drug responses varying among individuals according to a variety of... (Review)
Review
Anthelmintic drug efficacy (ADE) is generally estimated as a population average effect, despite drug responses varying among individuals according to a variety of measurable and non-measurable factors. Model-based and/or individual-level analyses are scarce and often methodologically frail. We propose that wider application of marginal and mixed models would offer benefits to the evaluation of ADE. We demonstrate, with a worked example, how model-based analyses: (i) capture the effects of correlation among hierarchically structured longitudinal data on estimates of ADE; (ii) permit robust inference on the association of measurable factors with ADE; and (iii) enable estimation of variation among individual-level estimates of ADE. The application of modelling approaches is discussed in the context of mass drug administration-based control of human helminthiases.
Topics: Animals; Anthelmintics; Helminthiasis; Humans; Linear Models; Models, Theoretical
PubMed: 25217844
DOI: 10.1016/j.pt.2014.08.004 -
International Journal of Molecular... Dec 2022Niclosamide is an FDA-approved anthelmintic drug for the treatment of parasitic infections. However, over the past few years, increasing evidence has shown that... (Review)
Review
Niclosamide is an FDA-approved anthelmintic drug for the treatment of parasitic infections. However, over the past few years, increasing evidence has shown that niclosamide could treat diseases beyond parasitic diseases, which include metabolic diseases, immune system diseases, bacterial and viral infections, asthma, arterial constriction, myopia, and cancer. Therefore, we systematically reviewed the pharmacological activities and therapeutic prospects of niclosamide in human disease and cancer and summarized the related molecular mechanisms and signaling pathways, indicating that niclosamide is a promising therapeutic player in various human diseases, including cancer.
Topics: Humans; Niclosamide; Neoplasms; Anthelmintics; Signal Transduction; Vascular Diseases
PubMed: 36555754
DOI: 10.3390/ijms232416116 -
Experimental Parasitology Oct 2022Haemonchus contortus is a highly pathogenic and prevalent helminth that causes many deaths in sheep herds. Anthelmintics are usually employed to overcome this issue;...
Haemonchus contortus is a highly pathogenic and prevalent helminth that causes many deaths in sheep herds. Anthelmintics are usually employed to overcome this issue; however, they do not guarantee immediate and lasting efficacy because of the occurrence of drug-resistant parasites. Among substances that are used in scientific studies for parasitic control, essential oils are known to have different pharmacological properties. However, they demonstrate instability owing to several factors, and therefore, nanoemulsification is considered an alternative to control the instability and degradability of these compounds. The objective of this study was to evaluate the cytotoxicity of nanoemulsions containing essential oil of Eucalyptus globulus against the blood of healthy sheep and to verify their activity against the parasite H. contortus in sheep. The results presented adequate nanotechnological characteristics (diameter 72 nm, PDI 0.2, zeta -11 mV, and acidic pH) and adequate morphology. Further, the corona effect and cytotoxic profiles of the free oil and nanoemulsion against blood cells from healthy sheep were evaluated. The tests results did not present a toxicity profile. For evaluating efficacy, we observed an important anthelmintic action of the nanoemulsion containing oil in comparison to the free oil; the results demonstrate a potential role of the nanoemulsion in the inhibition of egg hatchability and the development of larvae L1 to L3 (infective stage). Based on these results, we developed an important and potential anthelmintic alternative for the control of the parasite H. contortus.
Topics: Animals; Anthelmintics; Eucalyptus Oil; Haemonchiasis; Haemonchus; Larva; Oils, Volatile; Sheep; Sheep Diseases
PubMed: 35985513
DOI: 10.1016/j.exppara.2022.108345 -
Biomolecules Oct 2021Parasitic nematodes infect almost all forms of life. In the human context, parasites are one of the major causative factors for physical and intellectual growth... (Review)
Review
Parasitic nematodes infect almost all forms of life. In the human context, parasites are one of the major causative factors for physical and intellectual growth retardation in the developing world. In the agricultural setting, parasites have a great economic impact through a reduction in livestock performance or control cost. The main method of controlling these devastating conditions is the use of anthelmintic drugs. Unfortunately, there are only a few anthelmintic drug classes available in the market and significant resistance has developed in most of the parasitic species of livestock. Therefore, development of new anthelmintics with different modes of action is critical for sustainable parasitic control in the future. The drug development pipeline is broadly limited to two types of molecules, namely synthetic compounds and natural plant products. Compared to synthetic compounds, natural products are highly diverse, and many have historically proven valuable in folk medicine to treat various gastrointestinal ailments. This review focus on the use of traditional knowledge-based plant extracts in the development of new therapeutic leads, the approaches used as screening techniques, and common bottlenecks and opportunities in plant-based anthelmintic drug discovery.
Topics: Animals; Anthelmintics; Anti-Infective Agents; Biological Products; Drug Discovery; Drug Resistance; Humans
PubMed: 34680090
DOI: 10.3390/biom11101457 -
Parasite (Paris, France) 2022Increasing anthelmintic resistance (AR) in livestock has stimulated growing efforts to monitor anthelmintic effectiveness (AE) on livestock farms. On-farm assessment of... (Review)
Review
Increasing anthelmintic resistance (AR) in livestock has stimulated growing efforts to monitor anthelmintic effectiveness (AE) on livestock farms. On-farm assessment of AE relies on measuring the reduction in faecal egg count (FEC) following treatment; and if conducted rigorously, qualifies as a formal FEC reduction test (FECRT) for AR. Substantial research effort has been devoted to designing robust protocols for the FECRT and its statistical interpretation; however, a wide range of factors other than AR can affect FEC reduction on farms. These are not always possible to control, and can affect the outcome and repeatability of AE measurements and confound the on-farm classification of AR using FECRT. This review considers confounders of FEC reduction, focusing on gastrointestinal nematodes of ruminants, including host and parasite physiology and demography; pharmacokinetic variation between drugs, parasites and hosts; and technical performance. Drug formulation and delivery, host condition and diet, and seasonal variation in parasite species composition, can all affect AE and hence observed FEC reduction. Causes of variation in FEC reduction should be attenuated, but this is not always possible. Regular monitoring of AE can indicate a need to improve anthelmintic administration practices, and detect AR early in its progression. Careful interpretation of FEC reduction, however, taking into account possible confounders, is essential before attributing reduced FEC reduction to AR. Understanding of confounders of FEC reduction will complement advances in FECRT design and interpretation to provide measures of anthelmintic efficacy that are both rigorous and accessible.
Topics: Animals; Anthelmintics; Drug Resistance; Feces; Nematoda; Parasite Egg Count
PubMed: 35389336
DOI: 10.1051/parasite/2022017 -
Parasites & Vectors Jul 2022Infections by gastrointestinal nematodes cause significant economic losses and disease in both humans and animals worldwide. The discovery of novel anthelmintic drugs is...
BACKGROUND
Infections by gastrointestinal nematodes cause significant economic losses and disease in both humans and animals worldwide. The discovery of novel anthelmintic drugs is crucial for maintaining control of these parasitic infections.
METHODS
For this purpose, the aim of the present study was to evaluate the potential anthelmintic activity of three series of compounds against the gastrointestinal nematodes Trichuris muris and Heligmosomoides polygyrus in vitro. The compounds tested were derivatives of benzimidazole, lipidic aminoalcohols and diamines. A primary screening was performed to select those compounds with an ability to inhibit T. muris L motility by > 90% at a single concentration of 100 µM; then, their respective IC values were calculated. Those compounds with IC < 10 µM were also tested against the adult stage of T. muris and H. polygyrus at a single concentration of 10 µM.
RESULTS
Of the 41 initial compounds screened, only compounds AO14, BZ6 and BZ12 had IC values < 10 µM on T. muris L assay, showing IC values of 3.30, 8.89 and 4.17 µM, respectively. However, only two of them displayed activity against the adult stage of the parasites: BZ12 killed 81% of adults of T. muris (IC of 8.1 µM) and 53% of H. polygyrus while BZ6 killed 100% of H. polygyrus adults (IC of 5.3 µM) but only 17% of T. muris.
CONCLUSIONS
BZ6 and BZ12 could be considered as a starting point for the synthesis of further structurally related compounds.
Topics: Animals; Anthelmintics; Benzimidazoles; Nematoda; Nematospiroides dubius; Trichuris
PubMed: 35804427
DOI: 10.1186/s13071-022-05347-y -
International Journal For Parasitology.... Aug 2021Currently, only a few chemical drug classes are available to control the global burden of nematode infections in humans and animals. Most of these drugs exert their...
Currently, only a few chemical drug classes are available to control the global burden of nematode infections in humans and animals. Most of these drugs exert their anthelmintic activity by interacting with proteins such as ion channels, and the nematode neuromuscular system remains a promising target for novel intervention strategies. Many commonly-used phenotypic readouts such as motility provide only indirect insight into neuromuscular function and the site(s) of action of chemical compounds. Electrophysiological recordings provide more specific information but are typically technically challenging and lack high throughput for drug discovery. Because drug discovery relies strongly on the evaluation and ranking of drug candidates, including closely related chemical derivatives, precise assays and assay combinations are needed for capturing and distinguishing subtle drug effects. Past studies show that nematode motility and pharyngeal pumping (feeding) are inhibited by most anthelmintic drugs. Here we compare two microfluidic devices ("chips") that record electrophysiological signals from the nematode pharynx (electropharyngeograms; EPGs) ─ the ScreenChip™ and the 8-channel EPG platform ─ to evaluate their respective utility for anthelmintic research. We additionally compared EPG data with whole-worm motility measurements obtained with the wMicroTracker instrument. As references, we used three macrocyclic lactones (ivermectin, moxidectin, and milbemycin oxime), and levamisole, which act on different ion channels. Drug potencies (IC and IC values) from concentration-response curves, and the time-course of drug effects, were compared across platforms and across drugs. Drug effects on pump timing and EPG waveforms were also investigated. These experiments confirmed drug-class specific effects of the tested anthelmintics and illustrated the relative strengths and limitations of the different assays for anthelmintic research.
Topics: Animals; Anthelmintics; Caenorhabditis elegans; Humans; Ivermectin; Levamisole; Nematoda
PubMed: 34252686
DOI: 10.1016/j.ijpddr.2021.05.005 -
International Journal For Parasitology.... Dec 2020Anthelmintic resistance is a significant threat to livestock production systems worldwide and is emerging as an important issue in companion animal parasite management....
Anthelmintic resistance is a significant threat to livestock production systems worldwide and is emerging as an important issue in companion animal parasite management. It is also an emerging concern for the control of human soil-transmitted helminths and filaria. An important aspect of managing anthelmintic resistance is the ability to utilise diagnostic tests to detect its emergence at an early stage. In host-parasite systems where resistance is already widespread, diagnostics have a potentially important role in determining those drugs that remain the most effective. The development of molecular diagnostics for anthelmintic resistance is one focus of the Consortium for Anthelmintic Resistance and Susceptibility (CARS) group. The present paper reflects discussions of this issue that occurred at the most recent meeting of the group in Wisconsin, USA, in July 2019. We compare molecular resistance diagnostics with in vivo and in vitro phenotypic methods, and highlight the advantages and disadvantages of each. We assess whether our knowledge on the identity of molecular markers for resistance towards the different drug classes is sufficient to provide some expectation that molecular tests for field use may be available in the short-to-medium term. We describe some practical aspects of such tests and how our current capabilities compare to the requirements of an 'ideal' test. Finally, we describe examples of drug class/parasite species interactions that provide the best opportunity for commercial use of molecular tests in the near future. We argue that while such prototype tests may not satisfy the requirements of an 'ideal' test, their potential to provide significant advances over currently-used phenotypic methods warrants their development as field diagnostics.
Topics: Animals; Anthelmintics; Drug Resistance; Helminths; Humans; Livestock; Pathology, Molecular
PubMed: 33307336
DOI: 10.1016/j.ijpddr.2020.11.005