Use Of Ivermectin Research Articles

The Detrimental Effect of Pre-Treatment with Ivermectin on Myocardial Ischemia

Introduction: Ivermectin (IVM) is a broad-spectrum anti-parasitic agent with potential antibacterial, antiviral, and anti-cancer effects. There are limited studies on the effects of IVM on cardiovascular diseases, so the present study sought to determine the effects of pre-treatment with IVM on myocardial ischemia in both ex vivo and in vivo. Methods: In the ex vivo part, two groups of control and treated rats with IVM (0.2 mg/kg) were examined for cardiac function and arrhythmias by isolated heart perfusion. In the in vivo part, four groups, namely, control, IVM, Iso (MI), and Iso + IVM 0.2 mg/kg were used. Subcutaneous injection of isoproterenol (100 mg/kg/day) for 2 consecutive days was used for the induction of myocardial infarction (MI) in male Wistar rats. Then electrocardiogram, hemodynamic factors, cardiac hypertrophy, and malondialdehyde (MDA) levels were investigated. Results: The ex vivo results showed that administration of IVM induces cardiac arrhythmia and decreases the left ventricular maximal rate of pressure increase (contractility) and maximal rate of pressure decline (relaxation). The isoproterenol-induced MI model used as an in vivo model showed that cardiac hypertrophy were increased with no improvement in the hemodynamic and electrocardiogram pattern in the IVM-treated group in comparison to MI (Iso) group. However, the MDA level was lower in the IVM-treated group. Conclusion: IVM pre-treatment demonstrates detrimental effects in cardiac ischemia through exacerbation of cardiac arrhythmia, myocardial dysfunction, and increased cardiac hypertrophy. Therefore, the use of IVM in ischemic heart patients should be done with great caution.

COVID-19 Excess Deaths in Peru's 25 States in 2020: Nationwide Trends, Confounding Factors, and Correlations With the Extent of Ivermectin Treatment by State.

Introduction In 2020, nations hastened to contain an emerging COVID-19 pandemic by deploying diverse public health approaches, but conclusive appraisals of the efficacy of these approaches are elusive in most cases. One of the medicines deployed, ivermectin (IVM), a macrocyclic lactone having biochemical activity against SARS-CoV-2 through competitive binding to its spike protein, has yielded mixed results in randomized clinical trials (RCTs) for COVID-19 treatments. In Peru, an opportunity to track the efficacy of IVM with a close consideration of confounding factors was provided through data for excess deaths as correlated with IVM use in 2020, under semi-autonomous policies in its 25 states. Methods To evaluate possible IVM treatment effects, excess deaths as determined from Peruvian national health data were analyzed by state for ages ≥60 in Peru's 25 states. These data were compared with monthly summary data for excess deaths in Peru for the period 2020-2021 as published by the WHO in 2022. To identify potential confounding factors, Google mobility data, population densities, SARS-CoV-2 genetic variations, and seropositivity rates were also examined. Results Reductions in excess deaths over a period of 30 days after peak deaths averaged 74% in the 10 states with the most intensive IVM use. As determined across all 25 states, these reductions in excess deaths correlated closely with the extent of IVM use (p<0.002). During four months of IVM use in 2020, before a new president of Peru restricted its use, there was a 14-fold reduction in nationwide excess deaths and then a 13-fold increase in the two months following the restriction of IVM use. Notably, these trends in nationwide excess deaths align with WHO summary data for the same period in Peru. Conclusions The natural experiment that was put into motion with the authorization of IVM use for COVID-19 in Peru in May 2020, as analyzed using data on excess deaths by locality and by state from Peruvian national health sources, resulted in strong evidence for the drug's effectiveness. Several potential confounding factors, including effects of a social isolation mandate imposed in May 2020, variations in the genetic makeup of the SARS-CoV-2 virus, and differences in seropositivity rates and population densities across the 25 states, were considered but did not appear to have significantly influenced these outcomes.

COVID-19 and Ivermectin: Potential threats associated with human use.

Drugs re-purposing due to COVID-19 virus has declared a number of useful candidates for treatment and prevention of the virus. Ivermectin (IVM) has gained much popularity due to a strong background of magical applications against a broad spectrum of pathogens. The in- vitro studies of ivermectin have shown promise, the thorough clinical trials of its efficacy in the treatment and prevention of SARS-CoV-2 are still warranted. Useful strategies for analyzing projected use of IVM in human coronaviruses might be developed. It may be done by concluding ongoing clinical trials and culturing lessons from IVM usage in veterinary practice. The potential toxicity and careful dosage analyses are urgently required before declaring it as an anti-SARS-CoV-2 drug candidate. This manuscript overviews the background and potential threats associated with the off-label use of IVM as prophylactic drug or treatment option against COVID-19 virus.

Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro

Bovine respiratory disease (BRD) complex is an important viral infection that causes huge economic losses in cattle herds worldwide. However, there is no directly effective antiviral drug application against respiratory viral pathogens; generally, the metaphylactic antibacterial drug applications are used for BRD. Ivermectin (IVM) is currently used as a broad-spectrum anti-parasitic agent both for veterinary and human medicine on some occasions. Moreover, since it is identified as an inhibitor for importin α/β-mediated nuclear localization signal (NLS), IVM is also reported to have antiviral potential against several RNA and DNA viruses. Since therapeutic use of IVM in COVID-19 cases has recently been postulated, the potential antiviral activity of IVM against bovine respiratory viruses including BRSV, BPIV-3, BoHV-1, BCoV and BVDV are evaluated in this study. For these purposes, virus titration assay was used to evaluate titers in viral harvest from infected cells treated with non-cytotoxic IVM concentrations (1, 2.5 and 5 μM) and compared to titers from non-treated infected cells. This study indicated that IVM inhibits the replication of BCoV, BVDV, BRSV, BPIV-3 and BoHV-1 in a dose-dependent manner in vitro as well as number of extracellular infectious virions. In addition, it was demonstrated that IVM has no clear effect on the attachment and penetration steps of the replication of the studied viruses. Finally, this study shows for the first time that IVM can inhibit infection of BRD-related viral agents namely BCoV, BPIV-3, BVDV, BRSV and BoHV-1 at the concentrations of 2.5 and 5 μM. Consequently, IVM, which is licensed for antiparasitic indications, also deserves to be evaluated as a broad-spectrum antiviral in BRD cases caused by viral pathogens.

Ivermectin confers its cytotoxic effects by inducing AMPK/mTOR-mediated autophagy and DNA damage

Ivermectin (IVM), a broad-spectrum antiparasitic drug, is widely used in agriculture and animal husbandry. Due to widespread use and little metabolism in animals, the toxicity of IVM has received increasing attention. The accumulation of IVM in animal tissues and the excretion of urine and feces in the environment is the major source of potential toxicity. Human consumption of meat or milk contaminated with livestock can result in exposure to high levels of IVM exposure. The aim of this study was to reveal the cytotoxic mechanism of IVM in model cell HeLa in vitro, in order to provide a theoretical basis for the safe and rational use of IVM. Here we observed the γH2AX and 8-oxodG foci to detect the DNA damage in HeLa cells. As expected, we found that IVM can induce oxidative double-stranded damage in HeLa cells, indicating that IVM has potential genotoxicity to human health. In addition, we observed the formation of LC3-B in HeLa cells, the accumulation of Beclin1, the degradation of p62 and the activation of the AMPK/mTOR signal transduction pathway. This suggests that IVM confers cytotoxicity through autophagy mediated by the AMPK/mTOR signaling pathway. We conclude that IVM produces genotoxicity and cytotoxicity by inducing DNA damage and AMPK/mTOR-mediated autophagy, thereby posing a potential risk to human health.

Anthelmintic Efficacy and Pharmacokinetics of Ivermectin Paste after Oral Administration in Mules Infected by Cyathostomins.

Simple SummaryMules and donkeys are often treated as horses from a therapeutic point of view. This approach could be dangerous due to species differences in drug pharmacokinetics which could reflect on the drug effectiveness. Ivermectin is a commonly used anthelmintic compound due to the broad spectrum of activity. The improper use of ivermectin (i.e., dosage, route of administration) could cause a lack of parasite control and contribute to development of drug resistance. Studies on the pharmacokinetics and efficacy of antiparasitic molecules in mules are limited, although these drugs are crucial for the welfare of these equines. The aim of the present study was to evaluate the efficacy and pharmacokinetics of ivermectin administered to mules at the same dosage (200 µg/kg body weight) and route licensed for horses. Results show that administering ivermectin orally, at the same dosage of horses, has a pharmacokinetic intermediate behavior between horses and donkeys. This study demonstrates that ivermectin oral paste at horse dosage is effective and safe for the treatment of cyathostomins in mules.Ivermectin (IVM) is an anthelmintic compound commonly used off-label in mules due to its broad-spectrum of activity. Despite the general use of IVM in mules with the same dose and route of administration licensed for horses, significant pharmacokinetic differences might exist between horses and mules, as already observed for donkeys. The aim of the present study was to evaluate the pharmacokinetic profile and anthelmintic efficacy of an oral paste of IVM in mules naturally infected with cyathostomins. Fifteen adult mules with fecal egg counts (FEC) ≥ 200 eggs per gram (EPG), with exclusive presence of cyathostomins, were included in the study. All mules were orally treated with IVM according to the manufacturer's recommended horse dosage (200 µg/kg body weight). FECs were performed before (day-10 and day-3) and after treatment at days 14 and 28 by using a modified McMaster method. The FEC reduction (FECR%) was also calculated. Blood samples were collected from five animals at various times between 0.5 h up to 30 days post treatment to determine pharmacokinetic parameters. The maximum IVM serum concentration (Cmax) was 42.31 ± 10.20 ng/mL and was achieved at 16.80 ± 9.96 h post-treatment (Tmax), area under the curve (AUC) was 135.56 ± 43.71 ng × day/mL. FECR% remained high (>95%) until the 28th day.

Effects of ivermectin treatment during prepubertal and pubertal period on sexual parameters and sexual behavior in adulthood in rats

Pediculosis is a parasitic disease that is considered a serious global public health problem. It is caused by the ectoparasite that is popularly known as lice, mainly affecting children in early childhood. The most commonly used treatment to combat this parasitosis is the macrocyclic lactone ivermectin (IVM). However, the use of IVM is contraindicated in children who are younger than 5 years old or who weigh <15 kg because some types of drugs that are used during certain periods of brain maturation can lead to behavioral disorders. The present study evaluated the effects of IVM treatment during the prepubertal and pubertal period on sexual behavior in adulthood in male rats. Genital grooming, preputial separation, sexual behavior, sexual motivation, relative organ weight, the gonadosomatic index, and histopathology were evaluated. Oral dose of 0.2 mg/kg (therapeutic dose) of a commercial IVM formulation was administered. IVM affected genital grooming but did not influence preputial separation in prepubertal rats. Prepubertal IVM administration did not impair sexual behavior in adult rats, with the exception of the time of residence with female rats in the sexual motivation test. It did not affect relative organ weights, with the exception of the relative weight of the full seminal vesicle. It did not alter the gonadosomatic index, and no histopathological alterations were observed in different organs. These results indicate that administration of a therapeutic dose of IVM during the prepubertal and pubertal period does not alter parameters of sexual development or sexual behavior in adult male rats.

Onthophagus landolti and Canthon indigaceus chevrolati (Coleoptera: Scarabaeinae) are attracted to the feces of ivermectin-treated cattle in the Mexican tropics

Ivermectin (IVM) is widely used for parasite control in livestock in the tropics. Residual IVM in feces conserves its insecticide activity for weeks and can harm dung beetle (DB) species. Attraction to the feces of IVM-treated cattle was tested using the DB species Onthophagus landolti (Harold) and Canthon indigaceus chevrolati (Harold) as models. Experiments were done under controlled laboratory conditions, semi-controlled field conditions and uncontrolled field conditions. Olfactometers were used in the controlled and semi-controlled trials. The control treatment was baited IVM-free feces, and the experimental treatments were the feces of cattle treated with 1 % IVM (subcutaneous administration; single, 0.2 mg/kg bw dosage) and collected at 5, 14, 21 and 28 days post-treatment. The uncontrolled field trial involved pitfall traps baited with IVM-free feces or feces from IVM-treated cattle collected five days post-treatment. Under controlled and semi-controlled conditions, the feces of IVM-treated cattle (at 5, 14, 21 or 28 days post-treatment) attracted more O. landolti and C. i. chevrolati individuals than IVM-free feces (P &lt; 0.05). The same response occurred under uncontrolled conditions. This clear attraction for IVM-containing cattle feces by the studied DB species highlights that incorrect IVM use may pose a risk to DB communities in cattle production systems.

Avermectin treatment for Lepeophtheirus salmonis: Impacts on host (Salmo salar) and parasite immunophysiology

The avermectins, emamectin benzoate (EMB) and ivermectin (IVM) have been commonly used in North America over the last two decades to control the salmon louse, Lepeophtheirus salmonis, infections in farmed Atlantic salmon. Emamectin benzoate, trade name SLICE ™, was used heavily in the Eastern Canadian industry between the years 2000–2008, due to its long lasting protection and efficacy against all parasitic life stages. However, over reliance on this drug soon resulted in reduced sensitivity in many L. salmonis populations, resulting more recently in uses of higher treatment dosages and switching to the use of IVM. For these reasons, we investigated the effects of different dosages of EMB and multiple IVM treatments on baseline immunophysiological indicators, anti-viral responses and protection against subsequent salmon lice exposure in salmon smolts. Different doses of EMB or repeated treatment with IVM did not affect feeding behaviour in salmon, however by the end of the second IVM treatment, some neurotoxicity was observed. A single (1×) EMB dose (50 μg/Kg) administered for 7 consecutive days had no significant effect on L. salmonis abundance and development, whereas triple the dosage (150 μg/Kg) significantly reduced lice development, thereby eliminating subsequent stress responses in salmon associated with lice development to pre-adult stages. Emamectin benzoate and IVM treatment did not significantly impact expression of resting antigen presentation molecules in salmon (MH class I or II), however they did inhibit short-term (6 h) induced responses to the ISA virus. The impact of gender, as previously shown, had the greatest effect on louse transcriptomic regulation, but avermectin treatment also caused perturbations in gene expression. Transcriptome differences between lice on control and 1× EMB treated fish were larger than those observed for IVM or 3× EMB. Nearly half of the transcripts differentially expressed by IVM were also affected by one of the EMB treatments. Transcriptomic results from the louse suggest a high degree of similarity and concordance within and across studies in avermectin treatment, with gender of louse and dosage of drug significantly impacting the outcomes.

Determinación mediante prueba cometa del daño genético causado por uso de ivermectina en vacas cebú (Bos taurus indicus)

Objetivo. El objetivo del trabajo fue evaluar el daño genético causado por el uso de Ivermectina (IVM) en vacas cebú (Bos taurus indicus). Materiales y Métodos. Se tomaron quince vacas, con edad entre tres y cuatro años, peso promedio de 350 kilogramos, condición corporal entre 3 y 3,5. Se utilizaron tres grupos experimentales con cinco animales por grupo, los cuales se expusieron a la concentración de IVM al 1% y 3,15% más un grupo control (sin aplicación de IVM). La muestra sanguínea por animal fue realizada mediante punción venosa yugular o caudal medial con aguja para vacutainer ®, extrayéndose 8 ml de sangre. Las muestras sanguíneas fueron recolectadas a los 9, 18 y 27 días postratamiento. Resultados. La visualización de los cometas se realizaron con microscopio de fluorescencia, las células fueron evaluadas por medio de registro visual y por el software Comet Imagen. Se evidenció la presencia de núcleos con migración de ADN en todas las placas analizadas. Los valores de clasificación de los cometas, denotaron células con altos niveles de daño alto (grado 3). El índice de daño del ADN de los tratamientos al 1% y 3,15% fue significativo, al relacionarlo con el grupo control. Conclusión. Los resultados de este estudio evidenciaron el probable potencial genotóxico del uso de la IVM en ganado vacuno.

Evaluation of pharmacokinetics and efficacy of ivermectin following oral administration in dogs against experimental infection of Ctenocephalides felis felis and Rhipicephalus sanguineus

With the increasing number of pets in home the human-animal relationship is increasingly close and care about control disease growing. Ivermectin (IVM) is frequently used because its proven safety.IVM is recommended for the treatment of demodectic scabies and prevention of heartworm in dogs, but informally is extremely used to control of Ctenocephalides felis felis and Rhipicephalus sanguineus. The aim of this study is evaluate the use of IVM in dogs, by the oral route at 0.6μg/kg dose, against experimental infection of these parasites using the construction of the plasma concentration curve and efficacy study. A IVM quantification method in canine plasma using HPLC-FL was developed and validated based on RE n°899/03 ANVISA. The samples collected during the efficacy test was analyzed by this validated method and prove Cmax of 350ng/mL at 4h (tmax) and AUC of 8411ng/h/mL. Spite of formulation have shown good absorption, the highest efficiency values found for Rhipcephalus sanguineus and Ctenocephalides felis felis were very low, 35% and 67% respectively, demonstrating this not be the most appropriate treatment for the control of these parasites.

Ivermectin Pharmacokinetics, Metabolism, and Tissue/Egg Residue Profiles in Laying Hens.

The goals were to determine the ivermectin (IVM) plasma pharmacokinetics, tissue and egg residue profiles, and in vitro metabolism in laying hens. Experiments conducted were (1) 8 hens were intravenously treated with IVM and blood samples taken; (2) 88 hens were treated with IVM administered daily in water (5 days) (40 were kept and their daily eggs collected; 48 were sacrificed in groups (n = 8) at different times and tissue samples taken and analyzed); (3) IVM biotransformation was studied in liver microsomes. Pharmacokinetic parameters were AUC = 85.1 ng·day/mL, Vdss = 4.43 L/kg, and T1/2el = 1.73 days. Low IVM tissue residues were quantified with the highest measured in liver and skin+fat. IVM residues were not found in egg white, but significant amounts were quantified in yolk. Residues measured in eggs were greater than some MRL values, suggesting that a withdrawal period would be necessary for eggs after IVM use in laying hens.

Doxycycline Leads to Sterility and Enhanced Killing of Female Onchocerca volvulus Worms in an Area With Persistent Microfilaridermia After Repeated Ivermectin Treatment: A Randomized, Placebo-Controlled, Double-Blind Trial.

Ivermectin (IVM) has been the drug of choice for the treatment of onchocerciasis. However, there have been reports of persistent microfilaridermia in individuals from an endemic area in Ghana after many rounds of IVM, raising concerns of suboptimal response or even the emergence of drug resistance. Because it is considered risky to continue relying only on IVM to combat this phenomenon, we assessed the effect of targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline for these individuals with suboptimal response. One hundred sixty-seven patients, most of them with multiple rounds of IVM, were recruited in areas with IVM suboptimal response and treated with 100 mg/day doxycycline for 6 weeks. Three and 12 months after doxycycline treatment, patients took part in standard IVM treatment. At 20 months after treatment, 80% of living female worms from the placebo group were Wolbachia positive, whereas only 5.1% in the doxycycline-treated group contained bacteria. Consistent with interruption of embryogenesis, none of the nodules removed from doxycycline-treated patients contained microfilariae, and 97% of those patients were without microfilaridermia, in contrast to placebo patients who remained at pretreatment levels (P < .001). Moreover, a significantly enhanced number of dead worms were observed after doxycycline. Targeting the Wolbachia in O. volvulus is effective in clearing microfilariae in the skin of onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment. Strategies can now be developed that include doxycycline to control onchocerciasis in areas where infections persist despite the frequent use of IVM. ISRCTN 66649839.

Use of Ivermectin as Endoparasiticide in Tropical Cattle Herds Generates Resistance in Gastrointestinal Nematodes and the Tick Rhipicephalus microplus (Acari: Ixodidae).

The objective of the present study was to determine simultaneously the status of resistance against ivermectin (IVM) in gastrointestinal nematodes (GIN) and Rhipicephalus microplus (Canestrini, 1888) ticks in 12 cattle farms where IVM was used for the control of GIN in the Mexican tropics. Six farms had frequent use of IVM (≥ 4 times per year) and six farms had low frequency of IVM use (1-2 times per year). The fecal egg count reduction test and the larval immersion test were used to determine the resistant status of GIN and R. microplus against IVM, respectively. The results indicated that 100% of the surveyed farms had IVM-resistant GIN (reduction % from 0 to 67%). The genera involved were Haemonchus, Cooperia, Ostertagia, Trichostrongylus, and Oesophagostomum. Although the IVM was never used for the control of ticks, 50% of the surveyed farms presented GIN and R. microplus simultaneously resistant to IVM. Furthermore, two R. microplus populations showed high resistance ratio (RR) to IVM (farm TAT: RR50% = 7 and RR99% = 40.1; and farm SLS: RR50% = 2.4; RR99% = 11.0). A high frequency of IVM use (≥ 4 times per year) seemed to promote IVM resistance amongst R. microplus ticks compared with the farms with low frequency of IVM use (1-2 times per year; 66.6 vs. 25.0%, respectively). However, the number of surveyed farms was insufficient to show clear statistical inferences (odds ratio = 6.00; 95% CI = 0.341-105.5). The use of IVM for the control of GIN promoted simultaneously the development of IVM resistance in the GIN and R. microplus populations of the cattle herds surveyed.

Reproductive status of Onchocerca volvulus after ivermectin treatment in an ivermectin-naïve and a frequently treated population from Cameroon.

BackgroundFor two decades, onchocerciasis control has been based on mass treatment with ivermectin (IVM), repeated annually or six-monthly. This drug kills Onchocerca volvulus microfilariae (mf) present in the skin and the eyes (microfilaricidal effect) and prevents for 3–4 months the release of new mf by adult female worms (embryostatic effect). In some Ghanaian communities, the long-term use of IVM was associated with a more rapid than expected skin repopulation by mf after treatment. Here, we assessed whether the embryostatic effect of IVM on O. volvulus has been altered following frequent treatment in Cameroonian patients.MethodologyOnchocercal nodules were surgically removed just before (D0) and 80 days (D80) after a standard dose of IVM in two cohorts with different treatment histories: a group who had received repeated doses of IVM over 13 years, and a control group with no history of large-scale treatments. Excised nodules were digested with collagenase to isolate adult worms. Embryograms were prepared with females for the evaluation of their reproductive capacities.Principal FindingsOocyte production was not affected by IVM. The mean number of intermediate embryos (morulae and coiled mf) decreased similarly in the two groups between D0 and D80. In contrast, an accumulation of stretched mf, either viable or degenerating, was observed at D80. However, it was observed that the increase in number of degenerating mf between D0 and D80 was much lower in the frequently treated group than in the control one (Incidence Rate Ratio: 0.25; 95% CI: 0.10–0.63; p = 0.003), which may indicate a reduced sequestration of mf in the worms from the frequently treated group.Conclusion/SignificanceIVM still had an embryostatic effect on O. volvulus, but the effect was reduced in the frequently treated cohort compared with the control population.

Impact of ivermectin-resistant gastrointestinal nematodes in feedlot cattle in 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&lt;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.

Field tests demonstrating reduced activity of ivermectin and moxidectin against small strongyles in horses on 14 farms in Central Kentucky in 2007–2009

Efficacy of ivermectin (IVM) and moxidectin (MOX) against small strongyles was evaluated in horses (n=363) in field tests on 14 farms in Central Kentucky between 2007 and 2009. Most of the horses were yearlings but a few were weanlings and mares. The number of horses treated with IVM was 255 and those treated with MOX was 108. Horses on six farms were allotted into two groups. One group was treated with each of the two drugs, whereas horses on the other eight farms were treated with only one of the two drugs--IVM on six farms and MOX on two farms. Strongyle eggs per gram of feces (EPGs) compared to initial use of IVM and MOX returned almost twice as quickly after treatment of horses on all of the farms. IVM has been used much more extensively in this geographical area than MOX. Reduced activity of MOX was evident even on farms with rare or no apparent previous use of MOX but with probable extensive use of IVM.

Resistencia antihelmíntica de nematodos gastroentéricos en ovinos a febendazol e ivermectina en la región noroeste del estado de Tlaxcala

This experiment examined the problem of anthelmintic resistance in gastro-intestinal nematodes (GIN) to Ivermectin (IVM) and Febendazole (Fbz) in naturally infected sheep from Tlaxcala, Mexico. Twenty flocks were selected from three districts in Northern Tlaxcala: Calpulalpan (4), Nanacamilpa (10) and Hueytotlipan (6). Groups ranged from 10 to 14 sheep each and they were designed as follows: I), control, II) treated with Fbz at 5 mg per kg of body weight per os, and group (III) treated with IVM at 0.2 mg/kg of bodyweight by subcutaneous injection. Faecal samples were collected and nematode egg counting was estimated at days 0 and 14. Results were based on the faecal egg counts and from a flock management survey applied to farmers. The results showed that one flock was resistant to IVM, three flocks were classified as suspicious and sixteen flocks were susceptible. Moreover, infected sheep treated with Fbz did not show anthelmintic resistance, however, three flocks were suspicious and seventeen flocks were susceptible to this drug. On the other hand, the survey analysis showed that the frequency of anthelmintic treatments was 75 % to IVM, 65 % to Fbz and 45 % to Salicilanide. Besides, 55 % of experimental sheep were Merino-Dorset acquired from Australia, 75 % Suffolk, 10 % Hampshire, 10 % Cross-breed and 5 % Columbia, these last four breeds were acquired from local regions. Moreover, resistance to IVM appeared to be related to the frequent use of IVM and by infected sheep with GIN acquired from other regions.

Ivermectin imposes selection pressure on P-glycoprotein from Onchocerca volvulus: linkage disequilibrium and genotype diversity

Widespread use of ivermectin (IVM) as part of the Onchocerciasis Control Program (OCP) in West Africa could influence the evolution of the human filarial parasite Onchocerca volvulus. Use of IVM, in some areas for 15 years, may have restricted genetic diversity of O. volvulus, resembling effects attributed to a population bottleneck. Large population-based chemotherapy programmes, such as the OCP, may impose strong selection pressure on parasites and an examination of possible genetic selection by IVM in O. volvulus is warranted. IVM is a substrate for P-glycoprotein; a homologue from O. volvulus (OvPGP) has been linked with IVM sensitivity. Linkage disequilibrium (LD) patterns of 28 genetic markers spanning the OvPGP locus were examined in 4 O. volvulus populations from the Volta Region of Ghana, West Africa. Reduced gene diversity, increased heterozygosity and an increase in the number of markers not in Hardy-Weinberg equilibrium were associated with increasing IVM treatment. The number of regions in LD decreased with treatment and with time. However, between 1999 and 2002, seven regions of OvPGP were always in complete LD, while surrounding areas showed a reduction in genetic variation. The use of IVM for onchocerciasis control has imposed strong selection on O. volvulus populations, reducing genetic variation and disrupting LD.