Ivermectin Solution Research Articles

Topical Dexamethasone Counters Intravitreal Ivermectin-Induced Ocular Toxicity in a Rabbit Model

Purpose Systemic use of Ivermectin has been reported to incite blindness in humans and veterinary patients. This study was designed to investigate the systemic and intravitreal effect of Ivermectin on ocular and retinal health and its attenuation with topical Dexamethasone. Methods Systemic injection of Ivermectin@ 1.6 mg/kg S/C was administered, thrice a week for three weeks to New Zealand White rabbits (N = 4) with and without topical drops of Verapamil (N = 4). Pre and post-treatment ocular examination was conducted. At the end of three weeks the eyes were collected for histopathology. 0.2 ml of Ivermectin solution (1.6 mg/ml) was injected intravitreally in one eye of the rabbit (N = 8), Half the rabbits received 0.1% dexamethasone drops thrice daily for 7 days, while the controls received PBS. Pre and post-treatment, detailed examination was conducted, which included the Schirmer Tear test, Fluorescein staining, Intraocular pressure, slit lamp biomicroscopy and fundus photography. The retina was harvested for histopathological and tunnel assay. Results Systemic therapy with Ivermectin, with and without Verapamil did not incite any adverse response in the eye. Intravitreal Ivermectin evoked severe uveitis 4/4, cataract 3/4, corneal erosion 3/4 eyes and severe inflammatory response. Eyes that received dexamethasone were rescued from the adverse changes as demonstrated clinically, by histopathology and prevention of apoptosis. Conclusions Intravitreal Ivermectin incites severe inflammatory response. Topical dexamethasone counters the ocular toxicity incited by Ivermectin.

A rapid diagnosis and treatment of Ornithonyssus bacoti infection.

Mites serve as pathogens, allergens, or microbial containers, which can seriously damage the health of humans and animals. The substantial amount of mite species and their similar morphology make it complicated to identify and classify. Our mouse breeder incidentally noticed papular-type erythema with itching and peeling of the skin in several places, and an investigation revealed that this symptom was caused by an uncommon parasite that appeared on the skin and around the nest of the mice. By morphological observation, DNA extraction, PCR amplification, and DNA sequencing, we roughly identified the category of the parasite as a mite. Then, we designed a specific primer cox1, amplified and sequenced the mitochondrial cox1 gene fragment of the mite, calculated the intraspecific and interspecific differences, and reconstructed the phylogenetic tree for sequence alignment. Finally, this species was identified and named this Ornithonyssus bacoti-KF. According to the ivermectin gradient test, we found that 0.1mg/mL concentration of ivermectin solution was the most effective for mite removal in the bath, with no recurrence after 6months of treatment. Ornithonyssus bacoti, diagnosed by microscopic exam and confirmed by PCR amplification sequencing, was treated with ivermectin to control the rodent-borne parasite effectively.

Poultry red mite eradication potential of ivermectin and allicin combination treatment.

Existing treatments against poultry red mite (PRM; Dermanyssus gallinae) infestation have reduced efficacy or exhibit hazardous effects on chickens. Considering the economic importance of chickens, development of a safe and effective method for exterminating PRMs is necessary. Ivermectin and allicin are effective against some ectoparasites; however, their acaricidal efficacies against PRMs remain unknown. To evaluate individual and combined efficacies of ivermectin and allicin in exterminating PRMs. Different concentrations (0.10-1.0mg/mL) of ivermectin (1mL) were applied via dropping method in different insect culture dishes (ICDs), prior to transferring PRMs. For the spraying method, PRMs were transferred to ICDs, before spraying ivermectin (1mg/mL) solution (1mL). Further, the acaricidal effect of allicin on PRMs was evaluated by applying different concentrations (0.25-1.0mg/mL) of allicin (1mL). The combined acaricidal effects of ivermectin and allicin were analysed using four concentration combinations. PRM death rates were determined after 2h, 24h, 2 days, 5 days and 7 days of drug application. Ivermectin application (1mg/mL) exterminated 64% and 100% of PRMs on 1 and 5 days, respectively, and prevented their revival. Further, 0.5mg/mL ivermectin and 1mg/mL allicin individually exterminated 98% and 44% of PRMs, respectively, within 7 days of treatment. In combination, 0.5mg/mL ivermectin and 0.5mg/mL allicin exterminated 100% of PRMs within 5 d of treatment. The most effective combination was 0.25mg/mL ivermectin + 1.00mg/mL allicin. The efficacy of ivermectin-allicin combination in exterminating PRMs was demonstrated. This novel approach could be optimised for industrial applications.

Yeşil iguanalarda Hirstiellosis'e karşı ivermektin solüsyonunun etkinliği

Interest in green iguanas (Iguana iguana) as pet animals is increasing day by day. Compared to other pet animals, the diagnosis and treatment methods of reptilian diseases are limited. Considering that these diseases will also concern public health, new research is required. Hirstiellosis is a zoonotic ectoparasitic disease seen in green iguanas (Iguana iguana). Recommended therapies are mostly empirical, some of which can be low-impact or toxic. The objective of this study is to determine the effectiveness of ivermectin solution (5 mg/l) in the treatment of hirstiellosis and to provide preliminary data for further studies. Ivermectin solution was found to be effective in the treatment of three iguanas with the aforementioned disease, and no clinical side effects were found in the control examinations made at regular intervals.

Manipulation of Spray-Drying Conditions to Develop an Inhalable Ivermectin Dry Powder.

SARS-CoV-2, the causative agent of COVID-19, predominantly affects the respiratory tract. As a consequence, it seems intuitive to develop antiviral agents capable of targeting the virus right on its main anatomical site of replication. Ivermectin, a U.S. FDA-approved anti-parasitic drug, was originally shown to inhibit SARS-CoV-2 replication in vitro, albeit at relatively high concentrations, which is difficult to achieve in the lung. In this study, we tested the spray-drying conditions to develop an inhalable dry powder formulation that could ensure sufficient antiviral drug concentrations, which are difficult to achieve in the lungs based on the oral dosage used in clinical trials. Here, by using ivermectin as a proof-of-concept, we evaluated spray-drying conditions that could lead to the development of antivirals in an inhalable dry powder formulation, which could then be used to ensure sufficient drug concentrations in the lung. Thus, we used ivermectin in proof-of-principle experiments to evaluate our system, including physical characterization and in vitro aerosolization of prepared dry powder. The ivermectin dry powder was prepared with a mini spray-dryer (Buchi B-290), using a 23 factorial design and manipulating spray-drying conditions such as feed concentration (0.2% w/v and 0.8% w/v), inlet temperature (80 °C and 100 °C) and presence/absence of L-leucine (0% and 10%). The prepared dry powder was in the size range of 1–5 μm and amorphous in nature with wrinkle morphology. We observed a higher fine particle fraction (82.5 ± 1.4%) in high feed concentration (0.8% w/v), high inlet temperature (100 °C) and the presence of L-leucine (10% w/w). The stability study conducted for 28 days confirmed that the spray-dried powder was stable at 25 ± 2 °C/<15% RH and 25 ± 2 °C/ 53% RH. Interestingly, the ivermectin dry powder formulation inhibited SARS-CoV-2 replication in vitro with a potency similar to ivermectin solution (EC50 values of 15.8 µM and 14.1 µM, respectively), with a comparable cell toxicity profile in Calu-3 cells. In summary, we were able to manipulate the spray-drying conditions to develop an effective ivermectin inhalable dry powder. Ongoing studies based on this system will allow the development of novel formulations based on single or combinations of drugs that could be used to inhibit SARS-CoV-2 replication in the respiratory tract.

In vitro larvicidal activity of ivermectin and povidone-iodine against Oestrus ovis.

To assess the in vitro larvicidal activity of ivermectin and povidone-iodine (PVP-I) against Oestrus ovis, the most frequent cause of external ophthalmomyiasis. L1 O. ovis larvae were collected from the nasal boots of sheep slaughtered in local abattoirs and transferred onto Petri dishes containing mucosal tissue (25 larvae/dish). The larvicidal activity of the following formulations was tested: 1% ivermectin suspension in balanced sterile saline solution (BSSS), 1% ivermectin solution in propylene glycol, propylene glycol, 0.6% PVP-I in hyaluronic acid vehicle (IODIM®), and combination of ivermectin 1% solution and 0.6% PVP-I. One mL of each formulation was added to different Petri dishes containing the larvae. The time needed to kill the larvae was recorded. 893 larvae were tested. The median time needed to kill the larvae was 46, 44, 11, 6, and 10 minutes for Iodim®, ivermectin 1% suspension, propylene glycol, ivermectin 1% solution, and a combination of ivermectin 1% solution with 0.6% PVP-I, respectively. Kaplan-Meyer analysis disclosed that the survival curves were significantly lower in samples treated with ivermectin 1% solution, ivermectin 1% solution + 0.6% PVP-I, and propylene glycol than in samples receiving other treatments or BSSS. In this in vitro study, ivermectin 1% solution in propylene glycol, ivermectin 1% solution + 0.6% PVP-I, and propylene glycol alone showed a good, relatively rapid larvicidal activity against O. ovis larvae. Further experimental and clinical studies are necessary to establish whether, or not, these formulations may be considered as potential candidates for the topical treatment for external ophthalmomyiasis caused by O. ovis.

Topical ivermectin in the treatment of pediculosis capitis

Background: Head lice infestation is considered a prominent issue because of its worldwide distribution, especially among children. Millions of children are infested with pediculosis capitis every year. The increasing rate of lice infestation has been reported even in the developed countries due to the resistance to known pediculicides. Besides, the louse is a vector for serious diseases, such as epidemic typhus fever. Objective: The aim of this work was the search for a new cheap and effective drug for pediculosis capitis. 2% ivermectin solution, a promising novel drug used for endoparasite and ectoparasite infections, was used in this study. Materials and Methods: This was a clinical trial study. The in vitro study was carried out in a period of five months. Samples of nits and lice were collected from female patients of the Department of Dermatology and Venereology, Baghdad Teaching Hospital. The study was conducted during a period from October 2002 through November 2003. One hundred fifty children from four primary schools in Hayy Al-A’amel, Baghdad, participated in this part of the study. The preparation was applied to the children by the author. One hundred children were tested with ivermectin solution and fifty children with rectified spirit. The first part of the study involved a parasitological evaluation (in vitro study) of pediculicidal and ovicidal activity, in which 4% ivermectin solution was discontinued because of contact dermatitis. Therefore, 2% ivermectin solution was used instead. Pediculicidal and ovicidal activity was examined half an hour afterward. The second part of the study involved a clinical evaluation (in situ study) of 2% ivermectin solution for half an hour. Results: Topical 2% ivermectin solution in rectified spirit is a good pediculicidal (100%) and a good ovicidal (88%) drug with good therapeutic efficacy (82% after the first application, 90% after the second application) against pediculosis capitis. Conclusion: The study described a novel topical preparation for pediculosis capitis, which was proven effective and safe.

Safety and Efficacy of the Combined Use of Ivermectin, Dexamethasone, Enoxaparin and Aspirina against COVID-19 the I.D.E.A. Protocol

From the first outbreak in Wuhan (China) in December 2019, until today (05/28/2020), the number of deaths worldwide due to the coronavirus pandemic exceeded 2.5 millions. Only in Argentina, 50,000 deaths have been confirmed so far. There haven’t been so far any clear diagnostic pattern for this exceptional entity except unilateral skin involvement, early onset of symptoms, positive ANA and negative tests for Borrelia burgdorferi. Hence, we report a new case of a young Moroccan man. No treatment tested worldwide has shown unquestionable efficacy in the fight against COVID-19, according to W.H.O, NIH and NICE reports and accumulated data. Our proposal consists of the combination of drugs, based on the pathophysiology of the virus. We have designed a treatment called I.D.E.A., based on four affordable drugs already available on the pharmacopoeia in Argentina, on the following rationale: -Ivermectin (IVM) solution to lower the viral load in all stages of COVID-19. -Dexamethasone 4 mg injection, as anti-inflammatory drug to treat hyperinflammatory reaction to COVID-infection. -Enoxaparin injection as anticoagulant to treat hypercoagulation in severe cases. -Aspirin 250 mg tablets to prevent hypercoagulation in mild and moderate cases. Except for Ivermection oral solution, which was used in a higher dose than approved for parasitosis, all other drugs were used in the already approved dose and indication. Regarding Ivermectin safety, several oral studies have shown it to be safe even when used at daily doses much higher than those approved already. A clinical study has been conducted on COVID-19 patients at Eurnekian Hospital in the Province of Buenos Aires, Argentina. The study protocol and its final outcomes are described in this article. Results were compared with published data and data from patients admitted to the hospital receiving other treatments. None of the patient presenting mild symptoms needed to be hospitalized. Only one patient died (0.59% of all included patients vs. 2.1% overall mortality for the disease in Argentina today, 3.1% of hospitalized patients vs. 26.8% mortality in published data). I.D.E.A. protocol has proved to be a very effective alternative to prevent disease progression of COVID-19 when applied to mild cases, and to decrease mortality in patients at all stages of the disease with a favorable risk-benefit ratio.

Outbreak and Eradication of Tropical Rat Mite (Acari: Macronyssidae) in a European Animal Facility.

A zoonotic, opportunistic out-break of tropical rat mite Ornithonyssus bacoti [Acari: Macronyssidae; Ornithonyssus bacoti (Hirst)] in an animal facility, is described. Immunocompetent mice [Mus musculus (Linnaeus)] and rat [Rattus norvegicus (Berkenhout)] strains in a conventional health status facility suffered from scratching and allopecia and staff members suffered from pruritic, erythemato-papular lesions, presumed to be allergic in origin. O. bacoti was identified and treatment with a 0.1% ivermectin solution led to its complete erradication. Safety assessment revealed no signs of acute toxicity in any animal strain. Following this inexpensive strategy, 7 wk after the initial dose, samples were negative for the presence of acari. At the time of this report, 26 months after diagnosis, O. bacoti remains undetected.

Different Treatment Regimen for Eradication of Pinworm (Syphacia obvelata)Infection in Mice Colony

Syphacia obvelata infection was diagnosed in mice during routine health monitoring of rodent colony at Animal Facility, ILS-NISER, Bhubaneswar. Entire mice colony was treated with fenbendazole mixed in drinking water @70 mg/liter in combination with topical spray of injectable 0.1% ivermectin solution to arrest the disease. At the same time mice were isolated and grouped (n=18) to compare other treatment regimens using ivermectin (oral & spray) and fenbendazole (oral) and chalk out an effective therapeutic strategy for large rodent colonies. Use of cocktail of oral fenbendazole and 0.1% ivermectin spray was able to eradicate pinworm infection in mice colony but study with individual use of fenbendazole in drinking water was not able to treat the infection in group. Oral use of ivermectin was able to treat pin worm infection in mice but is not recommended for treatment due to its deleterious effects. Use of 0.1% ivermectin as spray alone resulted in complete eradication of Syphacia obvelata hence suggested to be safe and effective method for pin worm eradication in large rodent colonies.

Susceptibility of Aedes aegypti (Linnaeus) (Diptera: Culicidae) Immature Forms to Ivermectin

Several mosquito populations have already exhibited resistance to various insecticides, a situation that imposes many problems in vector control programs in many countries. Several studies have recently reported a decrease in the persistence of temephos, the main larvicide used to control Aedes aegypti in Brazil, suggesting that mosquito populations have acquired resistance to this organophosphate in several states. Dengue is one of the most important arthropod-borne diseases in the world and in Brazil thousands of dengue cases are notified annualy. In order to verify the effects of ivermectin, a semi-synthetic drug widely used for treatment of livestock parisitic diseases, on Aedes aegypti larvae of 3rd and 4th instar, the insects were submitted to concentrations of 1, 5 and 10 ppm of ivermectin solution during 5, 15, 10, 60 and 1440 minutes. After 24 hours of observations, mortality rates were scored. Loss of mobility, progressive paralysis and high mortality of larvae were recorded. Observations suggest that few minutes of contact with the insect is sufficient to cause intoxication. Increases in ivermectin concentration cause a progressive mortality in A. aegypti larvae. The values presented in the present study indicate that chemical treatment using ivermectin may be an alternative to the use of ivermectin in dengue control programs.

Severe Myocoptes musculinus infestation and treatment in laboratory mice

A contagious disease characterized with severe pruritis, weight loss and alopecia was observed in laboratory mice in Experimental Animal Breeding Unit in University of Akdeniz, Turkey, after recently transferring the animals from Israel. Twenty out of 100 mice were referred to the clinics of the Department of Internal Medicine, Faculty of Veterinary Medicine University of Mehmet Akif Ersoy, for a diagnosis. Alopecia and severe itching were observed all over the body, particularly on the abdominal area. Skin scrapings were obtained from affected sites of the skin for a parasitological examination. At the examination of the skin scrapings, treated with 10 % of potassium hydroxide, numerous mange agents and eggs were observed. Agents were diagnosed as Myocoptes musculinus according to their morphological characteristics. Five mice were euthanatized and examined pathologically. At the histopathological examination of the skin samples taken from alopecia and pruritic areas, numerous mange agents were seen in the tunnels in the epidermis. Mild inflammatory reaction including lymphocyte and neutrophil leukocytes were observed in the dermis. After diagnosis, mice were treated with ivermectin (Vilmectin) solution via drinking water (8 mg/L drinking water once a week for 3 wks). All animals were successfully recovered after the treatment

Ｉｖｅｒｍｅｃｔｉｎの皮下投与が奏効した重症播種性糞線虫症の１剖検例

We report a 49-year-old man who was a human T-cell leukemia virus type 1 (HTLV-1) carrier, born in Okinawa prefecture where both strongyloidiasis and HTLV-1 are endemic. He presented with fever, headache and urinary retention. On the basis of CSF examination and MRI findings, his condition was diagnosed as myelitis. He received methylprednisolone pulse therapy. He was transferred to our hospital due to severe paralytic ileus. Strongyloides stercoralis (S. stercoralis) was found in the duodenal stained tissue of a biopsy specimen. Ivermectin applied both orally and through enema were ineffective because of severe ileus and intestinal bleeding. Nine mg (200 microg/kg) of ivermectin solution was administered subcutaneously every other day for five days (total amount 45 mg). The S. stercoralis burden in the stool decreased and paralytic ileus gradually resolved. Three weeks after the resolution of S. stercoralis infection, purulent meningitis developed and acute obstructive hydrocephalus appeared. The hydrocephalus improved by ventricular drainage. Approximately three months after drainage, he died of incidental aspiratory pneumonia. Autopsy showed neither eggs nor larvae of S. stercoralis in the organs. In this case, the fourth reported case in the world, subcutaneous ivermectin injection was dramatically effective. We should consider a diagnosis of strongyloidiasis for any patient from Okinawa prefecture who was an HTLV-1 carrier presenting with unknown origin ileus after treatment of steroid therapy.

Comparative efficacy of pour-on and subcutaneous injection of ivermectin on Melophagus ovinus (L.) in Darab ecotype goats of Southern Iran

The efficacy of ivermectin was evaluated against Melophagus ovinus in Darab ecotype goats of Iran. Twenty-four healthy Iranian crossbreed male goats were randomly divided into three equal groups ( n = 8). An experimental infestation was induced in all animals of the three groups with 100 M. ovinus on the body of each animal. Groups 1 and 2 were treated with 1% ivermectin solution at a dosage of 0.5 mg/kg of body weight applied as a pour-on along the dorsal midline and 0.2 mg/kg subcutaneously, respectively; while group 3 was kept as control group. Seven days after infestation ivermectin was administered then the goats were observed for a period of 7 days. Body surface of each goat of three groups was inspected daily and decreases in M. ovinus were recorded. The rate of elimination in keds was assessed on the basis of decrease in keds count on the skin and hairs. The results revealed that complete absence of keds were observed in 6 and 7 days post-treatment with injection and pour-on routes, respectively. The results of present study showed that subcutaneous injection of ivermectin more rapidly eliminated M. ovinus than pour-on route. Both routes were 100% effective against this parasite in the goats. Ivermectin can be a drug of choice against M. ovinus in long-hair Iranian goats due to its high efficacy, easy applicability and wide safety margin.

Effect of ivermectin on the life cycle and larval fat body of Culex quinquefasciatus

The present work investigated the behavior, survival rate and lethal effect of 1.5 ppb ivermectin on Culex quinquefasciatus larvae, based on morphological and biological parameters, and possible alterations of their fat body. Changes in the number of eggs/egg mass and length of the larval stage were investigated. For this experiment, 600 larvae of 3rd and 4th instars of the mosquito were tested. The laid eggs were separated and the hatched larvae were counted. Some larvae submitted to 1.5 ppb ivermectin solution were used to prepare samples for histological study. Results obtained showed that ivermectin in a concentration of 1.5 ppb caused paralysis to the larvae with a mortality rate of 73.38%, mobilization of substances stored in the fat body and reduction of the number of egg laid in the adult stage.

Myiasis infestation: a rare complication of decubitus ulcer

Myiasis infestation is a rare complication of decubitus ulcer which in the case described was caused by Sarcophaga spp. The 32-year-old debilitated woman, having previously been treated for decubitus ulcer on her left heel, had a recurrence on the same heel in which there was a myiasis infestation. After removal of the larvae, the wound was irrigated by ivermectin solution and further medical and surgical treatment of the wound was carried out.

Ivermectin used in percutaneous drug injection method for the treatment of liver hydatid disease in sheep

Ivermectin is a macrocyclic lactone (avermectins) produced by the actinomycete Streptomyces avermitilis. In this experimental study, the effectiveness of intracystic injection of ivermectin was studied as a new approach of percutaneous treatment of cystic echinococcosis. Twelve naturally infected sheep were selected and divided into 2 subgroups: treatment group (n = 9) and control group (n = 3). In the treatment group, approximate volume of ivermectin solution needed to achieve an intracystic concentration of 10 microg/mL was injected into cysts, but in the control group, sterile distillated water was applied. No reaspiration was performed at all. In the following period of 6 months, repeated sonography revealed a significant decrease in cyst sizes and progressive solidification of the cysts in the treatment group. In the control group, volumes of the cysts were increased. No major complications occurred during or after the procedure. After 6 months, all sheep were killed and examined for macroscopic and microscopic changes. Pathologic examination in the treatment group showed pericyst hyalinization, inflammatory cells in the cyst wall, degeneration of laminated and germinal membrane, and necrotic material in the cyst cavity. No viable protoscolices or daughter cysts were observed. Percutaneous treatment of cystic echinococcosis with ivermectin as a scolicidal agent seems to be effective in this animal model.

Persistent efficacy of doramectin and ivermectin against experimental infestations of Sarcoptes scabiei var. suis in swine

Two studies were performed to compare the persistent efficacy of doramectin and ivermectin in swine experimentally infested with Sarcoptes scabiei var. suis. In the Study 1, 84 pigs were treated with doramectin, ivermectin, or saline solution on Day 0. Pigs were then challenged with mites on Days 0, 7, 14, 21, 28, 35, or 42. Weekly evaluations were performed for 5 weeks following challenge with mites. Weekly evaluations included physical examination for clinical signs of sarcoptic mange and collection of skin scrapings for determination of mite counts. In the Study 2, 80 pigs were treated with doramectin, ivermectin, or saline solution on Day 0, and challenged with mites on Days 3, 6, 9, 12, 15, 18, 21, 24, or 27. Weekly evaluations were performed for 6 weeks after challenge exposure. All negative-control (saline-treated) animals in both studies developed evidence of mite infestation. In the Study 1, doramectin prevented mite infestations 7 days longer than ivermectin. Results from the Study 2 indicated that the persistent efficacy of doramectin was 18 days on the basis of mite recovery. This was twice as long as the persistent efficacy of ivermectin, which was 9 days on the basis of mite recovery.

Ação "in vitro" do Ivermectin sobre ovos de Lagochilascaris Minor leiper, 1909

Ovos uterinos de fêmeas L. minor, obtidos por eliminação espontânea de abscessos cervicais da paciente W. M. R. (Pequizeiro-GO) - foram postos em contato com solução de Ivermectin nas concentrações de 50, 100, 150, 200 e 250 microgramas. Os resultados demonstraram que a droga em todas as concentrações utilizadas não impediu o desenvolvimento larvário. Entretanto, decorrida a embriogênese houve um processo de desvitalização da larva no interior do ovo caracterizado pela liberação de uma massa amorfa a partir do ovo embrionado. Em ovos do grupo controle houve eclosão de uma larva íntegra com todas as características estruturais de larva de Lagochilascaris.

Efficacy of topically administered ivermectin against chorioptic and sarcoptic mange of cattle.

The efficacy of topically administered ivermectin against Chorioptes bovis and Sarcoptes scabiei var bovis on cattle was evaluated in five studies involving a total of 68 cattle. Treatment with ivermectin solution at a dose rate of 500 micrograms/kg bodyweight topically once was fully effective against C bovis and S scabiei when applied to healthy skin. Efficacy against S scabiei was impaired when the formulation was applied over areas of severe lesions caused by this parasite, presumably due to reduced absorption of ivermectin.