High Doses Of Ivermectin Research Articles

Hematological Profile and Aminotransferase Activity in Kintamani Bali Puppies Injected with High Doses of Ivermectin

Pr Ivermectin toxicity is known to cause harmful side effects or even death in dogs intolerant to the medication. Intolerant dogs have a mutation in the MDR-1 (Multi-Drug Resistance) gene, so they lack the P-glycoprotein gene that removes drugs from the brain. Therefore, this study aimed to determine ivermectin toxicity in Kintamani Bali puppies by examining physiological responses based on hematological profiles and aminotransferase activity after a high-dose injection. A laboratory observational approach was used, and the samples were 25 healthy female Kintamani puppies based on a veterinary examination, aged 3-6 months, weighing 6.32 ± 1.18 kg, randomly divided equally into five treatment groups. The treatments included a placebo (1ml Aqua Pro Injection) as a control, as well as a single dose of ivermectin injection sequentially 200, 400, 800, and 1600 µg/kg subcutaneously. Blood samples were collected before treatment and after 7 and 14 days post-treatment. The hematologic parameters observed included levels of hemoglobin, erythrocytes, hematocrit, total leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, as well as blood biochemistry, namely aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. Observation results after 4 hours of administration of ivermectin at doses of 800 and 1600 µg/kg of puppies showed changes in behavior, restlessness, depression, tremors, mydriasis, hypersalivation, anorexia, and polydipsia. Meanwhile, the results of hematological examination on the seventh day after ivermectin treatment showed a trend of erythropenia, leukocytosis, a decrease in hemoglobin levels, and an increase in aminotransferase enzyme activity. This condition continued until day 14, but the physiological parameter values showed that the puppy’s condition gradually improved compared to the seventh day after treatment. There were significant differences in the blood profile, AST, and ALT of Kintamani puppies injected with ivermectin at doses of 800 and 1,600 ug/kg compared to controls on days 7 and 14 after and before treatment. It was concluded that high-dose ivermectin injections in Kintamani Bali puppies caused toxicity with clinical signs of erythropenia, decreased hemoglobin, leukocytosis, and increased aminotransferase activity.

CLINICAL SAFETY OF IVERMECTIN TREATMENT IN NILE TILAPIA, Oreochromis niloticus

Ivermectin belongs to the group of avermectins, a group of macrocyclic lactones produced by Streptomyces avermitilis, this drug is widely used in the treatment of endoparasitoses and ectoparasitosis in different species of mammals around the world. Based on this need to develop an adequate sanitary management of fish farms and the therapeutic importance of macrocyclic lactones, this study aimed to evaluate the clinical safety of ivermectin administered orally as part of the feed for Nile tilapia (O. niloticus). For this, 56 tilapias (O. niloticus), ±100g, were placed in 7 aquariums (n=8) with a capacity of 100 L of water, supplied with running water devoid of chlorine, with the following treatments being preserved: T0 (Control, untreated), T1 and T2 (treated with 125 and 625µg/kg-1 of ivermectin, respectively). Blood samples were collected for hemogram, leukogram and evaluation of serum biochemical parameters, in addition to organs such as spleen, liver and kidneys (cranial and caudal) for somatic evaluation. The results admired an increase in serum levels of ALT, AST and glycemia, a reduction in cholesterol and triglyceride values ​​at the highest dose, in addition to a decrease in total protein levels and liver somatic analysis. There was no change in hematological parameters, while the leukocyte profile indicated a significant increase in total leukocytes in treated tilapia with lymphocytosis and neutrophilia.. Therefore, treatment with high doses of ivermectin can harm the health of Nile tilapia, requiring additional studies to establish safe therapeutic protocols for these animals.

Evaluation of the scabicidal effect of a single dose of fluralaner in a rabbit model of crusted scabies

Recently, scabies was included in the WHO roadmap for neglected tropical diseases 2021–2030. Till now, ivermectin is the only available oral drug that is currently approved for treating crusted scabies in humans. Concerns regarding its efficacy and safety have prompted research efforts to find new alternatives. Our study aimed to evaluate the therapeutic effect of a single dose of fluralaner in cases of crusted scabies in comparison with that of repeated weekly high doses of ivermectin. For the in vitro study, twenty adult female mites were exposed to 50 μg/ml and 100 μg/ml ivermectin and fluralaner to evaluate their effects on mites' survival. For the in vivo study, thirty-five male crossbreed rabbits were divided into 4 groups: group I (non-infected, non-treated), group II (infected, non-treated), group III (infected and treated with ivermectin in a weekly oral dose of 0.4 mg/kg body weight/rabbit for 4 weeks, starting 8 weeks post-infection), and group IV (infected and treated with fluralaner given as a single oral dose of 25 mg/kg body weight/rabbit, starting 8 weeks post-infection). Clinical, parasitological, histopathological, and biochemical assessments were done. Clinical and parasitological assays were accomplished to all infected groups starting from day 0, then on days 2, 4, 6, 8, 10, 12, 14, 21, 28, 35, 42, 49 and 56 post-treatment, while histopathological and biochemical assessments were done at the end of the 8th week post-treatment (day 56). Our results showed that fluralaner exhibited a higher acaricidal effect on adult Sarcoptes scabiei var. cuniculi when compared with ivermectin applied in the same concentration (50 μg/ml or 100 μg/ml). Concerning the in vivo study, both clinical cure and parasitological cure were noted in both treated groups, evidenced by complete absence of all clinical signs of infestation and absence of mites in all skin scrapings. However, the ivermectin-treated group showed incomplete histopathological and biochemical resolution. Interestingly, both clinical cure and negative skin scrapings were noticed earlier in the fluralaner-treated group, with no apparent side effects. Also, no significant differences were noticed in the skin sections and serum biochemical parameters when compared with those of the negative control group. We concluded that fluralaner is a promising scabicidal agent that is recommended to be studied for possible human use, especially in control programs.Graphical abstract

Nematode resistance to ivermectin (630 and 700 μg/kg) in cattle from the Southeast and South of Brazil

Two high doses of ivermectin (630μg/kg and 700μg/kg) that are sold commercially in Brazil were evaluated in dose-and-slaughter trials with 144 naturally nematode-infected cattle from eight regions within the states of Minas Gerias, São Paulo and Rio Grande do Sul in Brazil. Treatment groups were based on fecal egg counts 1, 2, and 3days before treatment; all animals studied had a minimum egg count of at least 500 eggs per gram of feces (EPG). Post-mortem analyses were conducted on day 14. The highest levels of resistance to ivermectin were found for Haemonchus placei, Cooperia punctata and Oesophagostomum radiatum; all populations of H. placei were resistant to the 630μg/kg dose, and 67% were resistant to 700μg/kg; 86% of C. punctata were resistant to the 630μg/kg dose, and 33% were resistant to 700μg/kg. A combined analysis revealed that 57% of O. radiatum were resistant to the lower dose of ivermectin. H. placei, C. punctata and O. radiatum, in order, were the nematode populations with the highest indices of resistance, whereas Trichostrongylus axei was the most susceptible to 630 and 700μg/kg dosages of ivermectin. The results of helminthic resistance to ivermectin for different populations of H. placei and C. punctata described in the present study support previous literature data, in which a small decrease in the average parasitic burden of C. punctata and a consequent increase of H. placei were observed in cattle from the Southeast, South and Center-West regions of Brazil.

A randomized, double-blind, controlled trial of the effects of ivermectin at normal and high doses, given annually or three-monthly, against Onchocerca volvulus: ophthalmological results

A three-year randomized, controlled, double-blind trial was conducted in Cameroon to determine whether ivermectin, given at three-monthly intervals and/or at high doses (800 microg/kg), had a greater effect on adult Onchocerca volvulus than standard doses (150 microg/kg annually). As several patients complained of transitory subjective visual problems after treatment, some of them being of an unexpected type, we organized two series of detailed ophthalmological examinations to evaluate whether they were associated with ocular lesions. Analysis showed that these complaints were significantly more frequent in the two groups treated with high doses of ivermectin than in the reference group. In the ophthalmological examinations, the only differences recorded between the groups were a lower prevalence and mean number of microfilariae in the anterior chamber in the groups treated three-monthly, and, at the first examination round, a higher prevalence of early lesions of the iris in the group treated at high doses annually. These findings do not allow us to explain the cause of the transitory ocular complaints, nor why they were more frequent in the groups treated at high doses. However, one may conclude that using doses of ivermectin higher than the standard one should be considered with caution.

Adverse systemic reactions to treatment of onchocerciasis with ivermectin at normal and high doses given annually or three-monthly

In Cameroon, a 3-year randomized, double-blind controlled trial was conducted to determine if ivermectin, given at 3-monthly intervals and/or at high doses (800 μg/kg), had a greater effect on adult Onchocerca volvulus than standard annual doses of 150 μg/kg. Adverse reactions were recorded and analysed in a logistic regression model with random effects to assess the influence of the dose and rhythm of treatment on their occurrence. After the first dose, 3-monthly treatment was associated with a clearly reduced risk of reactions, especially oedematous swellings, pruritus and back-pain. Oedematous swellings and subjective ocular troubles were found to be associated with high doses of ivermectin. These results reinforce former parasitological conclusions that it would be desirable to evaluate the feasibility and effects on transmission of large-scale 3-monthly treatments with standard doses of ivermectin for onchocerciasis control. Owing to the unexpected ocular reactions, the use of high doses to counteract any future resistance of O. volvulus to ivermectin should be considered with caution.

River blindness.

Onchocerciasis, or river blindness, is caused by the filarial parasite Onchocerca volvulus. The disease has been a scourge of many of the poorest people in some of the least developed areas of the world. River blindness not only robs people of their sight during what should be the most productive periods of their lives, but also has rendered much of the arable lands of sub-Saharan Africa unavailable for agricultural use. The devastating socioeconomic effects of this disease have motivated the international community to implement three large programmes whose goal is to eliminate the disease. These programmes include the Onchocerciasis Control Programme in West Africa (OCP), the African Programme for Onchocerciasis Control (APOC), and the Onchocerciasis Elimination Program of the Americas (OEPA). Effects of standard and high doses of ivermectin on adult worms of Onchocerca volvulus: a randomised controlled trialTreatment with 3-monthly ivermectin could greatly reduce the number of female worms and acute itching and skin lesions; lower transmission of O volvulus; and change the duration of control programmes. Full-Text PDF

Comparison of High Dose Ivermectin and Diethylcarbamazine for Activity Against Bancroftian Filariasis in Haiti

This three-phase study was designed to compare high dose ivermectin with a standard diethylcarbamazine (DEC) regimen for patient tolerability, potential to kill adult filaria, and duration of microfilarial suppression in 30 Haitian subjects with Wuchereria bancrofti microfilaremia. All were first given a 1-mg oral dose of ivermectin (phase 1) to reduce microfilaria densities. Participants were randomized into three groups: Group 1 received DEC (6mg/kg per day for 12 days), Group 2 received 200 mcg/kg of ivermectin, and Group 3 received 400 mcg/kg of ivermectin (200 mcg/kg per day for 2 days). All drug regimens were well tolerated with few adverse reactions. Most reactions occurred during phase I and consisted primarily of headache, fever, and myalgia. At the end of phase 1, 27 of 30 (90%) patients were microfilaria negative. During phase 2, four of the six men receiving DEC developed scrotal reactions suggesting killing adult worms; no such reactions were noted in 10 men receiving ivermectin (p less than 0.05). At one-year follow up (phase 3), all treatment groups had less than 10% return to pretreatment microfilaria levels. The mean percent of baseline microfilaria counts were for Group 1, 0.9% (range 0-5%); Group 2, 8.2% (range 0-31%); and Group 3, 3.8% (range 0-25%). Seven individuals in Group 1 were microfilaria-negative, while only one and three individuals were microfilaria-negative in Groups 2 and 3, respectively. These results suggest that DEC causes more damage to the adult worms and greater reduction in microfilaria densities than ivermectin, but that high doses of ivermectin may suppress microfilaremia in lymphatic filariasis for periods much longer than previously reported.