DNA G-quadruplexes in the genome of Trypanosoma cruzi as potential therapeutic targets for Chagas disease: Dithienylethene ligands as effective antiparasitic agents.

Chagas disease is caused by the parasite Trypanosoma cruzi and affects over 7 million people worldwide. The two actual treatments, Benznidazole (Bzn) and Nifurtimox, cause serious side effects due to their high toxicity leading to treatment abandonment by the patients. In this work, we propose DNA G-quadruplexes (G4) as potential therapeutic targets for this infectious disease. We have found 174 PQS per 100,000 nucleotides in the genome of T. cruzi and confirmed G4 formation of three frequent motifs. We synthesized a family of 14 quadruplex ligands based in the dithienylethene (DTE) scaffold and demonstrated their binding to these identified G4 sequences. Several DTE derivatives exhibited micromolar activity against epimastigotes of four different strains of T. cruzi, in the same concentration range as Bzn. Compounds L3 and L4 presented remarkable activity against trypomastigotes, the active form in blood, of T. cruzi SOL strain (IC50 = 1.5-3.3 µM, SI = 25-40.9), being around 40 times more active than Bzn and displaying much better selectivity indexes.

Synthesis, characterisation, and in vitro antiparasitic activity of new flavanoidal tetrazinan-6'-ones and their binding study with calf thymus DNA using molecular modelling and spectroscopic techniques.

With the developing resistance to traditional antiparasitic medications, the purpose of this study was to efficiently develop a series of six noble flavanoidal tetrazinane-6'-one derivatives by a one-pot reaction pathway. FT-IR, 1HNMR, 13CNMR, and Mass spectra were employed for the structural elucidation of the synthesized compounds (7-12). Clinostomum complanatum, a parasite infection model that has been well-established, demonstrated that all the synthesized compounds are potent antiparasitic agents. DNA is the main target for various medicinal compounds. As a result, thestudy of how small molecules attach to DNA has received a lot of attention. In the present study, we have performed various biophysical techniques to determine the mode of binding of synthesized compounds (7-12) with calf thymus DNA (ct-DNA). It was observed from the UV-visible absorbance and fluorescence spectra that all synthesized compounds (7-12) form complexes with the ct-DNA. The value of binding constant (Kb) was obtained to be in the range of 4.36---24.50 × 103 M - 1 at 298 K. Competitive displacement assay with ethidium bromide (EB), CD spectral analysis, viscosity measurements, and in silico molecular docking confirmed that ligands (7-12) incorporate with ct-DNA through groove binding only. Molecular docking studies were performed for all synthesized compounds with the calf thymus DNA and it was found that all the newly synthesized compounds strongly bind with the chain B of DNA in the minor groove with the value of binding energy in the range of -8.54 to -9.04 kcal per mole and several hydrogen bonding interactions.

Lab-made CO2 laser-engraved electrochemical sensors for ivermectin determination.

The ivermectin (IVM), as a broad-spectrum antiparasitic drug, was widely prescribed to treat COVID-19 during the pandemic, despite lacking proven efficacy in combating this disease. Therefore, it is important to establish affordable devices in laboratories with minimal infrastructure. The laser engraving technology has been revolutionary in sensor manufacturing, primarily attributed to the diversity of substrates that can be employed and the freedom it provides in creating sensor models. In this work, electrochemical sensors based on graphene were developed using the laser engraving technology for IVM sensing. Through, the studies that used the techniques of cyclic voltammetry and differential pulse voltammetry, following parameter optimization, for the laser-induced graphene electrode demonstrated a mass transport governed by adsorption of the species and exhibited a linear working range of 10-100 (µmol L-1), a limit of detection (LOD) of 1.6 × 10-6 (mol L-1), a limit of quantification (LOQ) of 4.8 × 10-6 (mol L-1), and a sensitivity of 0.139 (µA µmol L-1). The developed method was successfully applied to direct analysis of pharmaceutical tablets, tap water (recovery of 94%) and synthetic urine samples (recovery between 97% and 113%). These results demonstrate the feasibility of the method for routine analyses involving environmental samples.

An Efficient and Scalable "Second Generation" Total Synthesis of the Marine Polyketide Limaol Endowed with Antiparasitic Activity.

The cluster of four skipped exo-methylene substituents on the "northern" wing of limaol renders this dinoflagellate-derived marine natural product unique in structural terms. This arguably non-thermodynamic array gains kinetic stability by virtue of populating local conformations which impede isomerization to a partly or fully conjugated polyene. This analysis suggested that the difficulties encountered during the late stages of our first total synthesis of this polyketide had not been caused by an overly fragile character of this unusual substructure; rather, an unfavorable steric microenvironment about the spirotricyclic core was identified as the likely cause. To remedy the issue, the protecting groups on this central fragment were changed; in effect, this amendment allowed all strategic and practical problems to be addressed. As a result, the overall yield over the longest linear sequence was multiplied by a factor of almost five and the material throughput increased more than eighty-fold per run. Key-to-success was a gold-catalyzed spirocyclization reaction; the reasons why a Brønsted acid cocatalyst is needed and the origin of the excellent levels of selectivity were delineated. The change of the protecting groups also allowed for much improved fragment coupling processes; most notably, the sequence of a substrate-controlled carbonyl addition reaction followed by Mitsunobu inversion that had originally been necessary to affix the southern tail to the core could be replaced by a reagent controlled asymmetric allylation. Finally, a much-improved route to the "northern" sector was established by leveraging the power of asymmetric hydrogenation of a 2-pyrone derivative. Limaol was found to combine appreciable antiparasitic activity with very modest cytotoxicity.

Design and Synthesis of 1,3-Diarylpyrazoles and Investigation of Their Cytotoxicity and Antiparasitic Profile.

Herein, we report a series of 1,3-diarylpyrazoles that are analogues of compound 26/HIT 8. We previously identified this molecule as a 'hit' during a high-throughput screening campaign for autophagy inducers. A variety of synthetic strategies were utilized to modify the 1,3-diarylpyrazole core at its 1-, 3-, and 4-position. Compounds were assessed in vitro to identify their cytotoxicity properties. Of note, several compounds in the series displayed relevant cytotoxicity, which warrants scrutiny while interpreting biological activities that have been reported for structurally related molecules. In addition, antiparasitic activities were recorded against a range of human-infective protozoa, including Trypanosoma cruzi, T. brucei rhodesiense, and Leishmania infantum. The most interesting compounds displayed low micromolar whole-cell potencies against individual or several parasitic species, while lacking cytotoxicity against human cells.

Discovery of 1,3,4-Oxadiazole Derivatives as Broad-Spectrum Antiparasitic Agents.

Vector-borne parasitic diseases (VBPDs) pose a significant threat to public health on a global scale. Collectively, Human African Trypanosomiasis (HAT), Leishmaniasis, and Malaria threaten millions of people, particularly in developing countries. Climate change might alter the transmission and spread of VBPDs, leading to a global burden of these diseases. Thus, novel agents are urgently needed to expand therapeutic options and limit the spread of drug-resistant parasites. Herein, we report the development of broad-spectrum antiparasitic agents by screening a known library of antileishmanial and antimalarial compounds toward Trypanosoma brucei (T. brucei) and identifying a 1,3,4-oxadiazole derivative (19) as anti-T. brucei hit with predicted blood-brain barrier permeability. Subsequently, extensive structure-activity-relationship studies around the lipophilic tail of 19 led to a potent antitrypanosomal and antimalarial compound (27), with moderate potency also toward Leishmania infantum (L. infantum) and Leishmania tropica. In addition, we discovered a pan-active antiparasitic molecule (24), showing low-micromolar IC50s toward T. brucei and Leishmania spp. promastigotes and amastigotes, and nanomolar IC50 against Plasmodium falciparum, together with high selectivity for the parasites over mammalian cells (THP-1). Early ADME-toxicity assays were used to assess the safety profile of the compounds. Overall, we characterized 24 and 27, bearing the 1,3,4-oxadiazole privileged scaffold, as broad-spectrum low-toxicity agents for the treatment of VBPDs. An alkyne-substituted chemical probe (30) was synthesized and will be utilized in proteomics experiments aimed at deconvoluting the mechanism of action in the T. brucei parasite.

Harnessing the 12 Green Chemistry Principles for Sustainable Antiparasitic Drugs: Toward the One Health Approach.

Antiparasitic drug development stands as a critical endeavor in combating infectious diseases which, by affecting the well-being of humans, animals, and the environment, pose significant global health challenges. In a scenario where conventional pharmacological interventions have proven inadequate, the One Health approach, which emphasizes interdisciplinary collaboration and holistic solutions, emerges as a vital strategy. By advocating for the integration of One Health principles into the R&D pharmaceutical pipeline, this Perspective promotes green chemistry methodologies to foster the development of environmentally friendly antiparasitic drugs for both human and animal health. Moreover, it highlights the urgent need to address vector-borne parasitic diseases (VBPDs) within the context of One Health-driven sustainable development, underscoring the pivotal role of medicinal chemists in driving transformative change. Aligned with the Sustainable Development Goals (SDGs) and the European Green Deal, this Perspective explores the application of the 12 Principles of Green Chemistry as a systematic framework to guide drug discovery and production efforts in the context of VBPD. Through interdisciplinary collaboration and a constant commitment to sustainability, the field can overcome the challenges posed by VBPD while promoting global and environmental responsibility. Serving as a call to action, scientists are urged to integrate One Health concepts and green chemistry principles into routine drug development practices, thereby paving the way for a more sustainable R&D pharmaceutical pipeline for antiparasitic drugs.

Exploring potential inhibitors of acetylcholinesterase, lactate dehydrogenases, and glutathione reductase from Hagenia abyssinica (Bruce) J.F. Gmel. based on multi-target ultrafiltration-liquid chromatography-mass spectrometry and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Parasitic infections impose a significant burden on public health worldwide. European pharmacopoeia records and ethnopharmacological studies indicate that Hagenia abyssinica (Bruce) J.F. Gmel. has traditionally been used to treat a variety of parasitic infections, while the potential antiparasitic compounds remain ambiguous. AIM OF THE STUDY: Acetylcholinesterase (AChE), lactate dehydrogenases (LDH), and glutathione reductase (GR) are the key target enzymes in the survival of parasites. The aim of our work was to screen antiparasitic compounds targeting AChE, LDH, and GR from H. abyssinica. MATERIALS AND METHODS: Ultrafiltration-liquid chromatography-mass spectrometry (UF-LC-MS) combined with molecular docking was used in this study. Therein, the alamarBlue® and Ellman's methods were employed to reveal the antitrypanosomal effect and AChE inhibitory activity. Meanwhile, the UF-LC-MS was carried out to screen the potential active compounds from H. abyssinica. Subsequently, molecular docking was performed to evaluate the binding mechanisms of these active compounds with AChE, LDH, and GR. Finally, the AChE inhibitory activity of potential inhibitors was detected in vitro. RESULTS: H. abyssinica exhibited significant antitrypanosomal and AChE inhibitory activity. Corilagin, brevifolin carboxylic acid, brevifolin, quercetin, and methyl ellagic acid were recognized as potential AChE inhibitors by UF-LC-MS, while methyl brevifolin carboxylate was identified as AChE, LDH, and GR multi-target inhibitor, with binding degree ranged from 20.96% to 49.81%. Molecular docking showed that these potential inhibitors had a strong affinity with AChE, LDH, and GR, with binding energies ranging from -6.98 to -9.67 kcal/mol. These findings were further supported by the observation that corilagin, quercetin, brevifolin carboxylic acid, and methyl brevifolin carboxylate displayed significant AChE inhibitory activity compared with the positive control (gossypol, 0.42 ± 0.04 mM), with IC50 values of 0.15 ± 0.05, 0.56 ± 0.03, 0.99 ± 0.01, and 1.02 ± 0.03 mM, respectively. CONCLUSIONS: This study confirms the antiparasitic potential of H. abyssinica, supporting the traditional use of H. abyssinica in local ethnopharmacology to treat parasites. At the same time, corilagin, brevifolin carboxylic acid, brevifolin, quercetin, methyl ellagic acid, and methyl brevifolin carboxylate exert their anti-parasitic effects by inhibiting AChE, LDH, and GR, and they are expected to be natural lead compounds for the treatment of parasitic diseases.

Bicyclic Pyrrolidine Inhibitors of Toxoplasma gondii Phenylalanine t-RNA Synthetase with Antiparasitic Potency In Vitro and Brain Exposure.

Previous studies have shown that bicyclic azetidines are potent and selective inhibitors of apicomplexan phenylalanine tRNA synthetase (PheRS), leading to parasite growth inhibition in vitro and in vivo, including in models of Toxoplasma infection. Despite these useful properties, additional optimization is required for the development of efficacious treatments of toxoplasmosis from this inhibitor series, in particular, to achieve optimal exposure in the brain. Here, we describe a series of PheRS inhibitors built on a new bicyclic pyrrolidine core scaffold designed to retain the exit-vector geometry of the isomeric bicyclic azetidine core scaffold while offering avenues to sample diverse chemical space. Relative to the parent series, bicyclic pyrrolidines retain reasonable potency and target selectivity for parasite PheRS vs host. Further structure-activity relationship studies revealed that the introduction of aliphatic groups improved potency and ADME and PK properties, including brain exposure. The identification of this new scaffold provides potential opportunities to extend the analogue series to further improve selectivity and potency and ultimately deliver a novel, efficacious treatment of toxoplasmosis.

Multitarget anti-parasitic activities of isoquinoline alkaloids isolated from Hippeastrum aulicum (Amaryllidaceae).

BACKGROUND: Chagas disease and leishmaniasis affect a significant portion of the Latin American population and still lack efficient treatments. In this context, natural products emerge as promising compounds for developing more effective therapies, aiming to mitigate side effects and drug resistance. Notably, species from the Amaryllidaceae family emerge as potential reservoirs of antiparasitic agents due to the presence of diverse biologically active alkaloids. PURPOSE: To assess the anti-Trypanosoma cruzi and anti-Leishmania infantum activity of five isolated alkaloids from Hippeastrum aulicum Herb. (Amaryllidaceae) against different life stages of the parasites using in silico and in vitro assays. Furthermore, molecular docking was employed to evaluate the interaction of the most active alkaloids. METHODS: Five natural isoquinoline alkaloids isolated in suitable quantities for in vitro testing underwent preliminary in silico analysis to predict their potential efficacy against Trypanosoma cruzi (amastigote and trypomastigote forms) and Leishmania infantum (amastigote and promastigote forms). The in vitro antiparasitic activity and mammalian cytotoxicity were investigated with a subsequent comparison of both analysis (in silico and in vitro) findings. Additionally, this study employed the molecular docking technique, utilizing cruzain (T. cruzi) and sterol 14α-demethylase (CYP51, L. infantum) as crucial biological targets for parasite survival, specifically focusing on compounds that exhibited promising activities against both parasites. RESULTS: Through computational techniques, it was identified that the alkaloids haemanthamine (1) and lycorine (8) were the most active against T. cruzi (amastigote and trypomastigote) and L. infantum (amastigote and promastigote), while also revealing unprecedented activity of alkaloid 7­methoxy-O-methyllycorenine (6). The in vitro analysis confirmed the in silico tests, in which compound 1 presented the best activities against the promastigote and amastigote forms of L. infantum with half-maximal inhibitory concentration (IC50) 0.6 µM and 1.78 µM, respectively. Compound 8 exhibited significant activity against the amastigote form of T. cruzi (IC50 7.70 µM), and compound 6 demonstrated activity against the trypomastigote forms of T. cruzi and amastigote of L. infantum, with IC50 values of 89.55 and 86.12 µM, respectively. Molecular docking analyses indicated that alkaloids 1 and 8 exhibited superior interaction energies compared to the inhibitors. CONCLUSION: The hitherto unreported potential of compound 6 against T. cruzi trypomastigotes and L. infantum amastigotes is now brought to the forefront. Furthermore, the acquired dataset signifies that the isolated alkaloids 1 and 8 from H. aulicum might serve as prototypes for subsequent structural refinements aimed at the exploration of novel leads against both T. cruzi and L. infantum parasites.

Antiparasitic efficacy of flavonoids identified from Psoralea corylifolia against Tetrahymena piriformis in guppy (Poecilia reticulate).

Tetrahymena piriformis belongs to the ciliated protists (ciliates), causing severe economic losses in aquaculture. Chemical drugs currently used usually have toxic side effects, and there is no specific drug against Tetrahymena. Therefore, it is an urgent need to identify new antiparasitic lead compounds. In the present study, the in vitro parasiticidal activity of ethyl acetate (EtOAc) extracts and water extracts from 22 selected traditional Chinese medicines (TCMs) were evaluated against T. piriformis. The EtOAc extract of P. corylifolia turned out to be the most active with the minimum parasiticidal concentration of 100 mg/L within 3 h. Thus, it was separated into 12 fractions by the first-dimensional (D1) normal phase liquid chromatography (NPLC), meanwhile combining with in vitro antiparasitic tests for activity tracking. Subsequently, 8 flavonoids were identified in the active fractions by the second-dimensional (D2) reverse phase liquid chromatography (RPLC) tandem high-resolution mass spectrometry. According to the results, 5 flavonoids were selected for in vitro antiparasitic test, of which isobavachalcone showed the minimum parasiticidal concentration of 3.125 mg/L in 2 h. Bathing treatment of infected guppies with isobavachalcone could significantly reduce the burden of T. piriformis, obtaining a 24-h median effective concentration (24-h EC50) value of 1.916 mg/L. And the concentration of isobavachalcone causing guppies to die within 24 h is 39 times than that of 24-h EC50. The results demonstrated that isobavachalcone has the potential to be developed into a novel commercial fish drug against T. piriformis.

Bioactivities and Structure-Activity Relationships of Usnic Acid Derivatives: A Review.

Usnic acid has a variety of biological activities, and has been widely studied in the fields of antibacterial, immune stimulation, antiviral, antifungal, anti-inflammatory and antiparasitic. Based on this, usnic acid is used as the lead compound for structural modification. In order to enhance the biological activity and solubility of usnic acid, scholars have carried out a large number of structural modifications, and found some usnic acid derivatives to be of more potential research value. In this paper, the structural modification, biological activity and structure-activity relationship of usnic acid were reviewed to provide reference for the development of usnic acid derivatives.

Therapeutic Potential of Marine-Derived Cyclic Peptides as Antiparasitic Agents.

Parasitic diseases still compromise human health. Some of the currently available therapeutic drugs have limitations considering their adverse effects, questionable efficacy, and long treatment, which have encouraged drug resistance. There is an urgent need to find new, safe, effective, and affordable antiparasitic drugs. Marine-derived cyclic peptides have been increasingly screened as candidates for developing new drugs. Therefore, in this review, a systematic analysis of the scientific literature was performed and 25 marine-derived cyclic peptides with antiparasitic activity (1-25) were found. Antimalarial activity is the most reported (51%), followed by antileishmanial (27%) and antitrypanosomal (20%) activities. Some compounds showed promising antiparasitic activity at the nM scale, being active against various parasites. The mechanisms of action and targets for some of the compounds have been investigated, revealing different strategies against parasites.

Pseudoxandra sclerocarpa maas, colombian medicinal plant: a review / Pseudoxandra sclerocarpa maas, planta medicinal colombiana: una revisión

The Annonaceae family is one of the largest, with 130 genre and 2500 species, consisting of trees, shrubs and a few vines. Within this family, the Pseudoxandra genus of neotropical distribution is found. In Colombia, there are endemic and native species, distributed in the Amazon region and along the valley of the Magdalena River in the Chocó. Of the total of 22 species that form the genus in Colombia, Pseudoxandra sclerocarpa Maas is exclusive of the Antioquia region, receiving the common name of garrapato or frisolo. From this tree, bisbenzylisoquinolinic alkaloids like antioquine, medellline, obaberine, among others, has been isolated. Also neolignans: dieugenol and dehydro-1-O-methydehydrodieugenol. It is used in traditional medicine as an antiparasitic. From the pharmacological point of view, the alkaloids have shown activity against leishmaniasis and also have spasmolytic activity. Within the bisbenzylisoquinolinic alkaloids, antioquine has properties of being calcium antagonist.

La familia Annonaceae es uno de los más grandes, con 130 géneros y 2.500 especies, que consiste en árboles, arbustos y algunos bejucos. Dentro de esta familia, el género Pseudoxandra es de distribución neotropical. En Colombia existen especies endémicas y nativas, distribuidas en la región del Amazonas ya lo largo del valle del río Magdalena en el Chocó. Del total de 22 especies que forman el género en Colombia, Pseudoxandra sclerocarpa es exclusiva de la región de Antioquia, recibiendo el nombre común de garrapato o frisolo. De este árbol se ha aislado alcaloides bisbencilisoquinolínicos como antioquina, medelllina, obaberina, entre otros. También neolignanos: dieugenol y dehidro-1-O-metil-dehidrodieugenol. Se utiliza en la medicina tradicional como un antiparasitario. Desde el punto de vista farmacológico, los alcaloides han mostrado actividad contra la leishmaniasis y también tienen actividad espasmolítica. Dentro de los alcaloides bisbencilisoquinolínicos, antioquina tiene propiedades de ser antagonista del calcio.

Impact of ivermectin-resistant gastrointestinal nematodes in feedlot cattle in Argentina / Impacto de nematódeos gastrointestinais ivermectina-resistentes em bovinos em confinamento na Argentina

The aim was to evaluate for 75 days the impact on production of the remaining burden of ivermectin (IVM)-resistant parasites in naturally infected feedlot calves. The herds came from tick-infested areas of cattle breeding where the systematic use of IVM to control tick increases the gastrointestinal parasites resistant to this drug. This investigation was carried out in two commercial feedlots in Buenos Aires province. In feedlot A, two groups of 35 animal each received IVM 1% and the other received ricobendazole (RBZ) 10% respectively. The same was done in feedlot B. On day 0, two groups of 35 animals were made in feedlots A and B. Fecal samples were taken on days 0, 22, 54 and 75 pos-treatment (PT), and body weight was registered, from each animal. Fecal samples were processed for individual count of eggs per gram (EPG) and pooled fecal culture was carried out for identification of the parasite genus in each sampling. Fecal egg count reduction test (FECR) was calculated on day 22 PT. The study design used was a totally randomized block, with commercial feedlot and sex as block variables. For data analysis, a mixed model of the SAS statistical program was used. The FECR average on day 22 was 28.4% in the IVM group, and 94,2 % in the RBZ group . From this date on, significant differences in EPG were kept until day 54. EPG counts were only equal near the end of the trial, on day 75 (p=0.16). In both commercial feedlots, especially in the IVM group, Cooperia spp. was the most prevalent parasite in the fecal cultures. Significant differences in weight (P<0.01) on post-treatment day 75 was found between the average weight in the RBZ and the IVM group (246 vs. 238 kg respectively), what means a difference of 8.3% in gains. The importance for production in the antiparasite failure treatment in commercial feedlots was demonstrated, and the need of pos-treatment controls to evaluate the efficacy of the antiparasitic administered is emphasized.

O objetivo deste trabalho foi avaliar durante 75 dias o impacto sobre a produção da carga de parasita-ivermectina (IVM) resistentes remanescentes em bezerros naturalmente infectados no confinamento. Os rebanhos são provenientes de áreas infestadas por carrapatos, onde o uso sistemático de IVM para o controle do carrapato aumenta a resistência de parasita gastrintestinais a esta droga. Este trabalho foi realizado em dois confinamentos comerciais na província de Buenos Aires. Na fazenda A, dois grupos de 35 animais cada receberam IVM 1% e ricobendazole (RBZ) 10%, respectivamente. O mesmo foi feito no confinamento B. No dia 0, dois grupos de 35 animais foram feitos nas fazendas A e B. As amostras fecais foram tomadas nos dias 0, 22, 54 e 75 pós-tratamento (PT) e o peso corporal foi registrado, de cada animal. Amostras fecais foram processadas para a contagem individual de ovos por grama (EPG). Amostras fecais foram agrupadas para a identificação do gênero parasitária. O teste de redução de ovos fecais (TROF) foi calculado no dia 22 PT. O desenho do estudo utilizado foi aquele dos blocos inteiramente randomizados, sendo confinamento comercial e sexo as variáveis de bloco. Para a análise dos dados, um modelo misto do programa estatístico SAS foi utilizado. A média TROF no dia 22 foi de 28,4% no grupo IVM e 94,2% no grupo RBZ. A partir desta data, diferenças significativas na EPG foram mantidas até o dia 54. Contas de OPG só foram iguais perto do fim do estudo, no dia 75 (p=0,16). Em ambos os confinamentos comerciais, especialmente no grupo IVM, Cooperia spp. foram os parasitos mais prevalentes nas culturas fecais. Diferenças significativas no peso (P<0,01) 75 dias pós-tratamento foram encontradas entre o peso médio nos grupos RBZ e IVM (246 vs 238 kg, respectivamente), o que significa uma diferença de 8,3% nos ganhos. A importância para a produção no tratamento da insuficiência antiparasitários em confinamento comercial foi demonstrada, bem como a necessidade de controles pós-tratamento para avaliar a eficácia dos antiparasitários administrados é enfatizada.