Antiparasitic Research Articles

River blindness: a devastating yet neglected tropical disease in Africa

River blindness is a Neglected Tropical Disease prevalent in Africa. It is transmitted through infected black flies that breed around fast-flowing rivers and streams. Over 120 million people in 31 African countries are at risk of contracting the disease, particularly in rural areas with limited healthcare access. Despite effective treatments being available, river blindness remains a major health issue. This is due to challenges in delivering treatment to remote areas, limited preventative measures and inadequate resources. Addressing this disease requires widespread distribution of ivermectin (antiparasitic drug) through mass drug administration programs. Vector control measures are also imperative to limit transmission. International collaboration and funding play a crucial role in the fight against river blindness in Africa; NGOs provide support for drug procurement and research. Strong partnerships between governments and various organizations play a pivotal role in potentially putting an end to this disease.

Metatranscriptomes-based sequence similarity networks uncover genetic signatures within parasitic freshwater microbial eukaryotes

BackgroundMicrobial eukaryotes play a crucial role in biochemical cycles and aquatic trophic food webs. Their taxonomic and functional diversity are increasingly well described due to recent advances in sequencing technologies. However, the vast amount of data produced by -omics approaches require data-driven methodologies to make predictions about these microorganisms’ role within ecosystems. Using metatranscriptomics data, we employed a sequence similarity network-based approach to explore the metabolic specificities of microbial eukaryotes with different trophic modes in a freshwater ecosystem (Lake Pavin, France).ResultsA total of 2,165,106 proteins were clustered in connected components enabling analysis of a great number of sequences without any references in public databases. This approach coupled with the use of an in-house trophic modes database improved the number of proteins considered by 42%. Our study confirmed the versatility of mixotrophic metabolisms with a large number of shared protein families among mixotrophic and phototrophic microorganisms as well as mixotrophic and heterotrophic microorganisms. Genetic similarities in proteins of saprotrophs and parasites also suggest that fungi-like organisms from Lake Pavin, such as Chytridiomycota and Oomycetes, exhibit a wide range of lifestyles, influenced by their degree of dependence on a host. This plasticity may occur at a fine taxonomic level (e.g., species level) and likely within a single organism in response to environmental parameters. While we observed a relative functional redundancy of primary metabolisms (e.g., amino acid and carbohydrate metabolism) nearly 130,000 protein families appeared to be trophic mode-specific. We found a particular specificity in obligate parasite-related Specific Protein Clusters, underscoring a high degree of specialization in these organisms.ConclusionsAlthough no universal marker for parasitism was identified, candidate genes can be proposed at a fine taxonomic scale. We notably provide several protein families that could serve as keys to understanding host-parasite interactions representing pathogenicity factors (e.g., involved in hijacking host resources, or associated with immune evasion mechanisms). All these protein families could offer valuable insights for developing antiparasitic treatments in health and economic contexts.7Frr3Q9Bret-L_FNz3hPRbVideo

Occurrence of gastrointestinal parasites in feces collected from stray dogs and in public parks in the city of Anápolis-Goiás

This study aimed to investigate the occurrence of gastrointestinal parasites in the feces of dogs and soil in public squares and parks in Anápolis. The presence of parasites in public squares and parks is primarily attributed to domesticated dogs that do not receive antiparasitic treatment and stray dogs, which can act as reservoirs for intestinal parasites with the potential to infect humans. Visceral Larva Migrans (VLM) and Cutaneous Larva Migrans (CLM) are of great importance when addressing gastrointestinal parasites, representing specific forms of parasitic infection that can affect humans. Additionally, other parasites such as Trichuris trichiura, Dipylidium caninum, and Giardia spp. are highlighted for their potential to cause intestinal infections. The transmission of these parasites is facilitated by improper human practices, such as handling food with dirty hands after contact with animals or contaminated soil. Of the 89 analyzed samples of shelter dog feces, 30.3% showed one or more parasites, with Toxocara canis being the most frequently found (24.7%). Associations between Ancylostoma sp and Toxocara canis were also observed in 3.37% of dogs. In the 105 feces soil samples collected in parks and squares, 29.5% tested positive, with emphasis on Ancylostoma canis. This underscores the importance of raising awareness among the population regarding the transmission of these parasites and the need to control the population of stray animals in public spaces, as well as the preventive deworming of dogs to reduce environmental contamination.

Avermectins Inhibit Replication of Parvovirus B19 by Disrupting the Interaction Between Importin α and Non-Structural Protein 1

Human parvovirus B19 (B19V) is a major human pathogen in which the ssDNA genome is replicated within the nucleus of infected human erythroid progenitor cells (EPCs) through a process involving both cellular and viral proteins, including the non-structural protein (NS)1. We previously characterized the interaction between NS1 classical nuclear localization signal (cNLS: GACHAKKPRIT-182) and host cell importin (IMP)α and proposed it as a potential target for antiviral drug development. Here, we further extend on such findings. First, we demonstrate that NS1 nuclear localization is required for viral production since introducing the K177T substitution in a cloned, infectious viral genome resulted in a non-viable virus. Secondly, we demonstrate that the antiparasitic drug ivermectin (IVM), known to inhibit the IMPα/β dependent nuclear import pathway, could impair the NS1-NLS:IMPα interaction and suppress viral replication in UT7/EpoS1 cells in a dose-dependent manner. We also show that a panel of structurally related avermectins (AVMs) can dissociate the NS1-NLS:IMPα complex with half-maximal inhibitory concentrations in the nanomolar range. Among them, Eprinomectin emerged as the most selective inhibitor of B19V replication, with a selectivity index of c. 5.0. However, when tested in EPCs generated from peripheral blood mononuclear cells, which constitute a cellular population close to the natural target cells in bone marrow, the inhibitory effect of IVM and Eprinomectin was demonstrated to a lesser extent, and both compounds exhibited high toxicity, thus highlighting the need for more specific inhibitors of the NS1-NLS:IMPα interaction.

Antileishmanial and Antitrypanosomal Trends of Synthetic Tetralone Derivatives.

Leishmaniasis and trypanosomiasis are parasitic diseases that are closely linked to poverty, pose significant local burdens, and are common in tropical and subtropical regions. Various synthetic tetralone derivatives were studied as potential scaffolds for antileishmanial and antitrypanosomal activities. The compounds were studied for their effectiveness against multiple kinetoplastid protozoan pathogens: Leishmania major, Leishmania mexicana, and bloodstream trypomastigotes of Trypanosoma brucei brucei. Two different strains of T. b. brucei were used. The first strain was the wild-type Trypanosoma brucei (s427-WT), and the second strain was the multidrug resistant (MDR) strain B48, which was produced by deleting the TbAT1 gene from s427WT and subsequent adaptation to high levels of resistance to diamidines and organo-arsenical drugs. Compounds 4c, 7c, 9b, and 11b showed activity against two strains of Trypanosoma and two different Leishmania species, establishing them as versatile leads with broad anti-kinetoplastid activity. Compound 4c, a tetralone derivative with a bromo-containing trimethoxybenzylidene moiety and methyl-substituted cyclohexanone ring, was identified as the most potent inhibitor for both T. b. brucei strains, with EC50 values of 0.19 and 0.22 µM for WT and B48, respectively, showing the absence of cross-resistance with the diamidine and arsenical trypanocide classes. In addition, compound 4c exhibited more potency than both controls, eflornithine and pentamidine, against the MDR strain. We conclude that tetralone derivates could be a valuable starting point for the discovery of new antiparasitic drugs.

Recombinant Methioninase (rMETase) Synergistically Sensitizes Ivermectin-resistant MCF-7 Breast Cancer Cells 9.9 Fold to Low-dose Ivermectin.

Ivermectin is a widely-used anti-parasitic agent and has shown early promise as an anticancer agent. Recombinant methioninase (rMETase) is a methionine-depleting enzyme targeting the methionine addiction of cancer and has broad efficacy against all tested cancer types. However, the combination efficacy of ivermectin and rMETase on breast cancer cells remains unexplored. The present study aimed to determine the synergistic efficacy of ivermectin and rMETase on MCF-7 human breast cancer cells in vitro. The IC10 of ivermectin and IC50 of rMETase were determined on MCF-7 cells using the WST-8 reagent to measure cell viability in vitro. MCF-7 cells were treated with four groups: untreated control; ivermectin alone (4.89 μM, IC10); rMETase alone (2.75 U/ml, IC50); and a combination of ivermectin (4.89 μM) and rMETase (2.75 U/ml). Cell viability was assessed 72 hours after treatment with the WST-8 reagent. Treatment with ivermectin (4.89 μM) did not significantly reduce the viability of MCF-7 cells. rMETase (2.75 U/ml) alone significantly reduced MCF-7 cell viability compared to the control group. The combination of ivermectin and rMETase resulted in a significantly greater reduction in cell viability than either agent alone, including a 9.9-fold greater efficacy than ivermectin alone, demonstrating synergistic efficacy (p<0.05). The combination of ivermectin and rMETase had synergistic efficacy against MCF-7 breast cancer cells in vitro. The present findings suggest that the combination of ivermectin and rMETase is a promising strategy for breast cancer requiring further preclinical and clinical evaluation.

Assessment of the Toxicological Effects of Cypermethrin Nanoformulation on &lt;i&gt;Hypselobarbus pulchellus&lt;/i&gt; using Selected Biomarkers

Pesticides are widely used in aquaculture farms against ectoparasites. However, due to the development of resistance in ectoparasites against the traditional pesticide formulations, pesticides are being applied at a higher dose or in combinations. Nano formulation of pesticides with enhanced properties is a viable option to reduce the volume of traditional pesticides applied in aquaculture. Hence, the present study developed a nano formulation of the pesticide cypermethrin and evaluated the toxic effects in the fish Hypselobarbus pulchellus. The acute toxicity study recorded the mortalities at 24h intervals for 96h. The 96h LC50 value was estimated to be 0.003 mg L-1. Chronic toxicity studies were also conducted exposing H. pulchellus to sublethal concentrations for 45 days. The brain acetylcholine esterase activity was significantly reduced (p ˂ 0.05) in the cypermethrin nano formulation exposed fish. The nano formulation exposure also caused a significant increase in the liver and kidney superoxide dismutase activity. Elevated catalase and glutathione-s-transferase levels were observed in the liver and gills, with no conspicuous change in the kidneys. The serum enzymes aspartate aminotransferase and alanine aminotransferase were elevated significantly by cypermethrin exposure. The serum triglycerides, cholesterol, and protein content were reduced significantly. Similarly, the red blood cell, haematocrit, haemoglobin, and platelet count also showed significant reduction on cypermethrin exposure. These findings on the toxic impacts may help to understand the effect of micro-formulated antiparasitic drugs in fin fish.

Treatment of Cestoda tapeworms using Peganum harmala: Review article

The human intestine is home to parasites called tapeworms. The term "tapeworm infection" describes this ailment. A larval cyst is the term for the young, dormant tapeworm. It is not limited to the intestine; it can also reside in other body areas. This illness is called cysticercosis or larval cyst infection. The symptoms of intestinal tapeworms are typically modest. Moderate to severe symptoms include diarrhea and stomach pain. Larval cysts can cause serious illness if they form in the brain, liver, lungs, heart, or eyes. Tapeworm infections can be treated with anti-parasitic medications, and larval cyst infections can be treated with anti-parasitic medications or surgically removing the cyst. Herbs and medicinal plants, such as Peganum harmala, which has safe and effective therapeutic capabilities without causing severe adverse effects to the human body and intestines, can be used as an alternative to chemical pharmaceuticals and to treat symptoms. Traditional medicines have been made from this well-known plant's seeds, bark, and root. P. harmala and its active alkaloids, harmine and harmaline, in particular, have shown a number of pharmacological and therapeutic benefits in recent years. According to analytical analyses of its chemical makeup, the most significant components of the plant are beta-carboline alkaloids, which include harmalol, harmaline, and harmine. Among these naturally occurring alkaloids, harmine has been investigated the most. These beta-carbolines are found in various other plants outside P. harmala, including Banisteria caapi, and are used to treat various illnesses.

P-1715. Antibiotic Stewardship based on the usage of Non- FDA Approved Fixed Dose Combination of Antibiotics in a Secondary Care Hospital South India

Abstract Background In developing countries, the widespread use of non-FDA (Food and Drug Administration) approved fixed-dose combinations of antibiotics in secondary care hospitals is a concern. Despite cautions from infectious disease specialists, comprehensive studies on this practice are lacking. Our research aims to investigate indications for prescribing these combinations in a South Indian secondary care hospital and develop stewardship strategies to reduce the use of it.TABLE 1:Indication for the Usage of non FDA Approved Fixed Combination of Antibiotics Methods The study conducted was a Prospective observational study at a secondary care hospital in South India over a 4-month period from December 2023 to March 2024. Data collection utilized a validated audit tool capturing details of non-FDA approved fixed dose antibiotic combinations prescribed to patients. Statistical analysis was conducted using MS Excel, employing simple descriptive statistics. Results CIPROFLOXACIN (500mg) + TINIDAZOLE (600mg) and CEFEXIME (200mg) + OFLOXACIN (200mg) are commonly prescribed for various conditions such as acute gastroenteritis, ear pain, and other ailments like fissures, cysts, and vaginal white discharge. However, these combinations lack FDA approval and randomized controlled trials (RCTs) to support their efficacy in treating conditions like otitis media and loose stools. The addition of antiparasitic agents in these combinations lacks evidence of effectiveness. Therefore, caution is advised in their prescription until further scientific validation is available. Conclusion In conclusion, our antibiotic stewardship efforts led to the removal of CIPROFLOXACIN (500mg) + TINIDAZOLE (600mg) and CEFEXIME (200mg) + OFLOXACIN (200mg) from our hospital formulary. Physicians were informed that these combinations lack scientific rationale for treating specific conditions. This action aligns with evidence-based prescribing practices to optimize patient care and combat antimicrobial resistance. Disclosures All Authors: No reported disclosures

Zinc from an Essential Element to an Antiparasitic Therapeutic Agent.

Tropical parasitic diseases affect millions of people around the world, particularly in poor countries. The human parasitic diseases that will be covered in this review are malaria and neglected diseases, such as leishmaniasis, Chagas disease, and African trypanosomiasis. The current treatments for these diseases present several problems, such as the development of drug resistance, very limited drugs available in the clinic, significant side effects of the drugs, and a long treatment period. For these reasons, there is an urgent need to develop new chemotherapeutics to eradicate or eliminate these diseases. Zinc-based drugs against parasitic diseases could be an alternative therapy to overcome the difficulties of the approved metallodrugs as antiparasitic agents. Zinc-based drugs are becoming an exciting field of research because zinc is an essential element that can lead to the development of multitarget antiparasitic agents, which are reviewed here.

ВЛИЯНИЕ КОНТАМИНИРОВАННОГО МИКОТОКСИНАМИ КОРМА И ПРОТИВОПАРАЗИТАРНОЙ ОБРАБОТКИ ЭПРИНОМЕКТИНОМ НА КИШЕЧНУЮ МИКРОБИОТУ ЖИВОТНЫХ В УСЛОВИЯХ ЭКСПЕРИМЕНТА

Animals are exposed to numerous stress factors in industrial conditions. The greatest danger is posed by mycotoxins that change the composition of the microbiota in animals, which is one of the reasons for the development of immunosuppression. The purpose of the study is to establish changes in the composition of the intestinal microbiota in laboratory animals with combined contamination of feed with mycotoxins and antiparasitic treatment with eprinomectin. The study was conducted on laboratory rats (five groups of 10 rats each). Animals of the 1st group received a standardized diet and were not exposed to mycotoxins and eprinomectin, the 2nd, 3rd, 4th and 5th groups of animals received food containing mycotoxins (DON – 0.93, T-2 – 0.025; ZEA – less than 0.02 mg/kg). Additionally, animals of the 3rd and 5th groups were subjected to a single antiparasitic treatment with the drug Veteprin (active ingredient – eprinomectin). Enterosorbent modified with polyarginine was administered daily with food to animals of groups 4 and 5 at a dose of 0.2 g/kg for 12 days at the final stage of the experiment lasting 50 days. The material for bacteriological research was samples of the contents of the cecum. The luminal microflora of the cecum in all animals is dominated by Bifidobactererium spp. and Lactobacillus spp. However, a noticeable decrease in their number is observed with the combined effect of eprinomectin and mycotoxins on the animal body, which indicates a decrease in colonization resistance and inhibition of parietal digestion. Against the background of a decrease in the proportion of obligate anaerobic microflora in the intestine, the number of facultative opportunistic microorganisms increases. Increased growth of yeast-like fungi in the intestine indicates decreased immune reactivity and impaired intestinal barrier function. The use of a sorbent modified with polyarginine normalizes and stabilizes the intestinal microflora.

АНАЛИЗ АНТИГЕЛЬМИНТНЫХ СРЕДСТВ ДЛЯ ВЕТЕРИНАРНОГО ПРИМЕНЕНИЯ

The paper presents the assortment trend and marketing analysis of veterinary medicinal products for the prevention and treatment of helminthic infestations in horses registered in the Russian Federation. Anthelmintics are antiparasitic drugs for the fight against helminths. The analysis of these drugs was carried out on the example of the veterinary pharmacies "Horsevet" and "Vetlek". According to the data obtained, it was established that the Russian market has a significant range of medicinal anthelmintic drugs (41 names) used for the prevention and treatment of helminth infections in horses. The domestic manufacturer occupies a leading position among the presented range of products – 34.1±1.87 %. On the market of veterinary drugs, there are imported anthelmintic drugs represented by such manufacturing countries as Belarus, Argentina, Brazil, Holland, Spain, Canada, etc. In the study of drugs by the number of pharmacologically active substances, it was found that monocomponent drugs account for 63.4±0.38 %, and multicomponent drugs – 36.6±0.85 %. The most common are soft dosage forms – 63.4±3.78 % (26 trade names in the form of flavored pastes and gels), which makes it easier to give the drug. Anthelmintic drugs in most cases are potent drugs, so most of them have a number of contraindications for use (85.4±4.95 %). 14.6±0.95 % of drugs have no contraindications. The use of all registered anthelmintic drugs for horses at the recommended doses does not cause changes in vital functions in the animal body.

Anthelmintic Potential of Annona muricata Leaf Extract against Parasitic Nematode Haemonchus contortus

Gastrointestinal infections caused by the parasitic worm Haemoncus contortus are the main cause of economic losses in the agricultural sector. H. contortus causes small ruminants such as goats to experience acute anemia and diarrhea, weight loss, decreased productivity, and eventually mortality, which impacts economic losses. Synthetic antiparasitics have been used extensively around the world to combat haemonchosis. However, the emergence of resistance to anthelmintics, accompanied by the unavailability of an effective vaccine, results in difficulties in controlling this disease. Because of the high cost of treatment and the emergence of resistance and toxicity due to the residue of antiparasitic drugs, it is necessary to develop natural anthelmintics that are easy to obtain, economical, and have minimal risk. This study aims to determine the anthelmintic effect of Annona muricata leaf extract on mice infected with H. contortus larvae. First, an in vitro study was conducted to see if the soursop leaf extract from Lombok would show a different effect from the previous research. In the in vivo test, the impact of A. muricata leaf extract was measured from the number of H. contortus eggs found in the feces and the percent reduction of adult worms collected from mice's stomachs. The result shows that the higher the concentration of soursop leaf extract, the higher the inhibition effect on larvae motility. The combination of A. muricata and albendazole had the strongest antiparasitic effect, shown by the lowest amount of eggs in feces and the highest reduction of adult worms in the stomach. However, administering A. muricata leaf extract can also reduce the number of eggs and adult worms in the stomach. Therefore, it can be concluded that A. muricata is a potential anthelmintic candidate for overcoming the H. contortus infection.

Knowledge, attitudes and practices of Australian dairy goat farmers towards the control of gastrointestinal parasites

BackgroundGastrointestinal parasites such as nematodes and coccidia are responsible for significant economic losses in the goat industry globally. An indiscriminate use of antiparasitic drugs, primarily registered for use in sheep and cattle, in goats has resulted in drug-resistant gastrointestinal parasites. Very little is known about the gastrointestinal parasite control practices used by Australian dairy goat farmers that are pivotal for achieving sustainable control of economically important parasites. The study reported here provides insights into gastrointestinal parasite control practices of Australian dairy goat farmers based on responses to an online survey.MethodsThe questionnaire comprised 58 questions on farm demography, husbandry and grazing management, knowledge of gastrointestinal parasites and their importance in dairy goats, diagnosis of infections, antiparasitic drugs and alternate control options. After a pilot survey (n = 15 respondents), a link to the questionnaire was available to all (n = 456) registered members of the Dairy Goat Society of Australia Ltd from 17 April to 16 June 2023. Multiple correspondence analyses (MCA) were performed to explore the association between selected parasite control practices.ResultsA total of 66 (14%) respondents completed the questionnaire. Of these, 74% (49/66) observed parasite-related illnesses in their goats; two-thirds of them assessed worms burden using faecal egg counts (FECs), with 26% (39/149) deworming their goats based on the results of the FECs. Most respondents (97%; 183/188) perceived that gastrointestinal parasites caused production losses and ranked Haemonchus contortus as the most important parasite. Anitparasitic drugs were used by 94% (62/66) of respondents, with the most frequently used anthelmintics being a commercial combination of four anthelmintics (levamisole, closantel, albendazole and abamectin), benzimidazoles and macrocyclic lactones. Most respondents (77%; 51/66) were unaware of anthelmintic resistance on their property. MCA results delineated two clusters of gastrointestinal parasites management.ConclusionsThis study provides insights into the demography of Australian dairy goat farms, the husbandry and grazing practices used by dairy goat farmers, their knowledge regarding gastrointestinal parasites and their practices for internal parasite control, thereby paving the way for tackling drug resistance in gastrointestinal parasites in dairy goats.Graphical

In vitro evaluation of anthelmintic activity of biocompatibile carbon quantum dot nanocomposite against egg and larval stages of equine strongyles

BackgroundStrongyle nematodes pose a major challenge in veterinary parasitology, causing significant economic losses in livestock due to resistance to conventional treatments. Current anthelmintics, like Ivermectin, often encounter resistance issues. This study aims to address these gaps by synthesizing Carbon Quantum Dots (CQDs) and Copper-Doped CQDs (Cu@CQDs) using glucose extract, and evaluating their nematicidal properties against strongyles in vitro. We assessed the nematicidal effects of CQDs and Cu@CQDs through larval feeding inhibition of first-stage larvae (L1), egg hatch inhibition (EHI), and the mobility and mortality of infectious larvae (L3s). Additionally, we conducted ultrastructural examinations of eggs and larvae and evaluated oxidative/nitrosative stress indicators, including total antioxidant status (TAS), protein carbonylation (PCO), lipid peroxidation (MDA), and oxidative DNA damage in homogenized samples of L3s.ResultsThe synthesized CQDs displayed semi-spherical morphology with diameters under 30 nm. Cu@CQDs at 12.5 µg/ml achieved over 90% EHI and larval motility inhibition. Fluorescence microscopy confirmed over 90% larval feeding inhibition at the same concentration. Both CQDs and Cu@CQDs induced oxidative stress, indicated by decreased TAS and increased MDA, PCO, and oxidative DNA damage. Scanning Electron Microscopy showed that CQDs and Cu@CQDs penetrated the larvae cuticle, altered the tegument, caused larval mortality, and resulted in egg deformities.ConclusionsGiven the potential for resistance to Ivermectin, seeking suitable alternatives is essential. Cu@CQDs exhibit effects similar to Ivermectin, indicating their potential as novel antiparasitic agents against strongyles. These findings emphasize the importance of exploring alternative treatments to address resistance and enhance nematode control efficacy.Graphical

Biosafety and Withdrawal Period of In-Feed Administered Antiparasitic Drug Emamectin Benzoate in Cirrhinus mrigala (Hamilton, 1822).

Parasitic infestations are one of the most economically important disease conditions in the Indian major carps including mrigal, Cirrhinus mrigala. This study reported the biosafety and tissue withdrawal of in-feed administered antiparasitic drug, emamectin benzoate (EMB). To evaluate the biosafety of the drug, behaviour, growth and tissue changes in Cirrhinus mrigala was recorded the following in-feed administration of EMB up to 10 times (T1-50 μg kg-1 fish day-1 (1×), T2-125 μg kg-1 fish day-1 (2.5×), T3-250 μg kg-1 fish day-1 (5×), T4-375 μg kg-1 fish day-1 (7.5×) and T5-500 μg kg-1 fish day-1 (10×)) for the period of three times the recommended duration (7 days). The withdrawal period was calculated by feeding EMB at 50 μg kg-1 fish day-1 for consecutive 10 days followed by EMB-free feed. The results revealed that the drug is safe to mrigal up to ten times the recommended dose, while the fish fed with the highest dose (500 μg kg-1 fish day-1) showed transient histological alterations. The feeding behaviour is affected with poor acceptability beyond 5× dosages. The drug residue at the concentration below the MRL (1.0 μg g-1) in the muscle tissue on the day of cessation of medicated feed administration indicates no requirement of the withdrawal period. The study suggests that EMB can be safely used at 50 μg kg-1 fish day-1 for 7 consecutive days, and no withdrawal period is required without affecting the feeding behaviour and tissue histological alterations.

Classification and Mechanism of Action of Anti-Parasitic Drugs: A Review Article

The action of antiparasitic drugs is critical in the treatment of infections caused by parasites and that have devastating effects on millions of individuals worldwide. This paper consolidates different research findings on the classification and mechanisms of action of these drugs, highlighting new therapies and natural products. In particular, this special class of heterocyclic compounds, known as Benzimidazoles, has garnered a wide interest in medicinal chemistry due to their broad pharmacological activities. It recognizes the important contribution normally made by these drugs in the treatment of a wide range of different diseases, including cancer, bacterial infection, and parasitic disease. Drug-resistant parasites are now increasingly prevalent and have greatly impeded the management of parasitic infections; thus, there is an increasing demand for new therapeutic approaches. Anti-parasitic metallodrugs have emerged as another auspicious mode of intervention that carefully exploits the unique chemical features of metal ions and their complexes to affect the biological pathways important for the survival of the parasite. In this paper, we will draw up a range of knowledge gaps identified up-to-date and propose future research directions that would enhance the understanding and, what is more important, the efficiency of anti-parasitic therapies.

Does intranasal demodex infestation play a role in chronic allergic rhinitis?

Aims: The aim of this study is to evaluate the prevalence of Demodex mites in the intranasal follicles of patients with allergic rhinitis and investigate their potential role in the etiology of allergic rhinitis. Methods: The study involved 50 patients diagnosed with allergic rhinitis and 50 healthy controls matched for age and gender. The severity of the disease was evaluated using the Score for Allergic Rhinitis and the Total Nasal Symptom Score (TNSS). To evaluate the presence of Demodex in nasal follicles, a total of 8 terminal follicles, 4 from each of the right and left nasal vestibules, were epilated using sterile forceps. The samples were examined under a light microscope at 10x, 40x, and 100x magnification by two dermatologists. Results: Demodex mites were found in the intranasal follicles of 3 (6%) individuals from the healthy control group. Intranasal Demodex mites were found in 3 (6%) patients with allergic rhinitis, showing no statistically significant difference between the two groups (p=1). The mean total nasal symptom score was 7.66±1.52 in the 3 allergic rhinitis patients with Demodex positivity, and 7.61±1.13 in the 47 patients without Demodex infestation, with no statistically significant difference between the two groups (p&amp;gt;0.05). No significant correlation was observed between Demodex positivity, disease severity, and TNSS in patients with allergic rhinitis (p&amp;gt;0.05). Conclusion: Based on our study results, we think that intranasal antiparasitic treatments may be unnecessary in patients with allergic rhinitis.

Reproductive management: conditioning, spawning and development of Peruvian grunt Anisotremus scapularis in southern Peru.

The Peruvian grunt, Anisotremus scapularis, is beginning its domestication as a candidate species for marine aquaculture. The optimal management of fingerling production requires precise knowledge on early development. Herein, we report the methodology for capturing and conditioning wild specimens to find a viable broodstock. The speed of capture and transportation (about 30 min), the post capture preventive treatment (60 min with tetracycline), and the 6-days preventive antiparasitic treatment (29 ppm formalin) maximized survival and a rapid feeding adaptation. Progressive diets based on the copepod Emerita analoga, fish meal, pellets and processed feedstuff prompted the spontaneous broodstock spawning 7 months post-capture. The interannual spawning of this broodstock since September 2016 indicated the optimal control of its reproduction in captivity. The morphogenetic process of the embryo lasted 42 h at 18 °C compared to (31-41) h at 19 °C in northern Peruvian latitudes. The knowledge generated allowed us to work out broodstock and egg management protocols in southern Pacific latitudes (southern Peru and northern Chile). Such protocols would help to escalate larval and juvenile production and to alleviate fishing pressure on the overexploited Peruvian grunt population.

The Ivermectin Related Compound Moxidectin Can Target Apicomplexan Importin α and Limit Growth of Malarial Parasites.

Signal-dependent transport into and out of the nucleus mediated by members of the importin (IMP) superfamily is crucial for eukaryotic function, with inhibitors targeting IMPα being of key interest as anti-infectious agents, including against the apicomplexan Plasmodium species and Toxoplasma gondii, causative agents of malaria and toxoplasmosis, respectively. We recently showed that the FDA-approved macrocyclic lactone ivermectin, as well as several other different small molecule inhibitors, can specifically bind to and inhibit P. falciparum and T. gondii IMPα functions, as well as limit parasite growth. Here we focus on the FDA-approved antiparasitic moxidectin, a structural analogue of ivermectin, for its IMPα-targeting and anti-apicomplexan properties for the first time. We use circular dichroism and intrinsic tryptophan fluorescence measurements to show that moxidectin can bind directly to apicomplexan IMPαs, thereby inhibiting their key binding functions at low μM concentrations, as well as possessing anti-parasitic activity against P. falciparum in culture. The results imply a class effect in terms of IMPα's ability to be targeted by macrocyclic lactone compounds. Importantly, in the face of rising global emergence of resistance to approved anti-parasitic agents, the findings highlight the potential of moxidectin and possibly other macrocyclic lactone compounds as antimalarial agents.