Systemic Ivermectin Research Articles

Detection of a knockdown mutation in the voltage-sensitive sodium channel associated with permethrin tolerance in Sarcoptes scabiei var. hominis mites.

Increasing evidence has sparked a debate on the loss of sensitivity of scabies mites to conventional permethrin therapy. Mutations in the voltage-sensitive sodium channels (VSSC) were associated with knockdown resistance (kdr) in many arthropods, but have never been identified in Sarcoptes scabiei variatio (var.) hominis mites. To identify factors contributing to therapy failure. Sixty-seven mites were collected from 64 scabies-infested patients in Vienna, Austria, of whom 85.9% were refractory to prior permethrin-based treatments, and genotyped for the presence of nucleotide polymorphisms in Domain II of the VSSC, known to be associated with kdr. Information regarding previous antiscabietic therapies, decontamination procedures and possible re-infestations by contacts as well as the response to re-imposed therapies were obtained. Sequence alignment comparisons revealed previously unidentified mutations in the coding region of Domain II of the VSSC. A novel A1663T transversion was detected in 97.0% of the mites, resulting in a non-synonymous substitution from methionine to leucine, M918L, a mutation known to confer kdr in other arthropods. In addition, a synonymous G1659A transition was identified in one mite, which otherwise showed a nucleotide sequence identical to the wild-type reference. No major inconsistencies were observed within the previous therapeutic and decontamination procedures, which could have accounted for the observed non-responsiveness to permethrin-based therapies. Subsequent cure of infestation was achieved in 65.6% of the participants, predominantly by combination therapies with topical permethrin and systemic ivermectin. However, in 14.6% of the cured cases, permethrin monotherapy sufficed for eradication of scabies, albeit in some cases prolonged exposure was necessary. The kdr-associated M918L mutation in the VSSC gene has now emerged in S. scabiei var. hominis mites. Hence, loss of sensitivity to permethrin due to kdr-type resistance may be more prevalent than anticipated and may be decisive for the therapy responsiveness of scabies-infested patients.

Treatment of oral myiasis in a patient with implant-supported fixed prosthesis

Oral myiasis is a rare parasitic disease that requires immediate treatment once diagnosed. However, no standard treatment protocol can be found in the literature. Through a clinical-surgical report, we present the case of an 82-year-old man with lesions extending through the vestibule and alveolar ridge of the maxilla on both sides, in addition to occupying a large part of the palate, with a considerable number of larvae. The patient was initially treated with a single dose of systemic ivermectin (6 mg orally) and topical application of a tampon soaked in ether. The larvae were then surgically removed and debridement of the wound was performed. A crushed tablet of ivermectin 6 mg was applied topically for 2 days, the remaining larvae were again mechanically removed, and the patient received intravenous antimicrobial therapy. Treatment with systemic and topical ivermectin combined with antibiotic therapy and debridement proved to be effective in treating oral myiasis.

Severe cutaneous adverse reactions associated with systemic ivermectin: A pharmacovigilance analysis.

Despite poor evidence, the antiparasitic ivermectin has been advocated as a potential COVID‐19 therapy. This has led to a rise in calls to poison‐control centers by people self‐medicating with ivermectin, which is sold over the counter for veterinary uses. We aimed to investigate the association between severe cutaneous adverse reactions (SCARs) and ivermectin. Postmarketing data from the FDA Adverse Event Reporting System (FAERS), gathered between 2014 and 2021, was employed to detect disproportional signals of SCARs following systemic ivermectin therapy. The reporting odds ratio (ROR) was used to quantify the strength of association, while adjusting for age, sex, and region. The search yielded 517 reports of systemic ivermectin (median age 54 years, 46.8% female), of which 25 (4.8%), 81 (15.7%), and 411 (79.5%) were classified as SCARs, nonsevere cutaneous adverse events (AEs), or noncutaneous AEs, respectively. The regional distribution differed between SCAR reports (32.0% from Africa and 12.0% from North America) compared with other AEs, which originated from North America in over half of cases. The most common SCARs were toxic epidermal necrolysis (seven cases), Stevens–Johnson syndrome (seven cases), and drug reaction with eosinophilia and systemic symptoms (four cases). Five SCAR cases (20.0%) resulted in death and 12 (48.0%) lead to hospitalization. There was a strong safety signal for any SCAR (adjusted ROR 3.34, 95% confidence interval [CI] 2.17–5.12) and toxidermias (adjusted ROR 7.08, 95% CI 4.23–11.84). This study suggests that ivermectin is associated with SCARs on rare occasions. Dermatologists should be aware of this given the increase in ivermectin misuse.

Scabies: Epidemiology, Diagnosis, and Treatment.

Scabies is a skin infestation whose incidence is apparently rising. This review is based on pertinent articles retrieved by a selective search of PubMed on diagnosis and treatment strategies. Thread-like papules (burrows), new, intense pruritus, and dermatitis guide the suspected diagnosis which is confirmed by the microscopic or dermatoscopic demonstration of scabies mites. The first line therapy is topical application of permethrin, in accordance with the current recommendations for its use. Other treatment options include systemic ivermectin and topical crotamiton or benzyl benzoate. A combination of permethrin and ivermectin is used to treat otherwise intractable cases and is generally indicated for the treatment of crusted scabies. Known causes of treatment failure include improper application of the external agents, failure of repeated treatment with ivermectin, incomplete decontamination of furnishings and clothes, failure to simultaneously treat contact persons, absence of written documents explaining treatment modalities, and the patient's belonging to a risk group. Even though there has not yet been any direct proof of resistance of scabies mites to permethrin, there is a rising number of welldocumented cases of poor response to this agent. Moxidectin is a new substance now undergoing clinical testing. Treatment of scabies according to the guidelines and the additional recommendations reported here should result in effective curing, even in cases that are thought to be intractable.

Management of an outbreak of invasive Kingella kingae skeletal infections in a day care center

BackgroundKingella kingae (Kk) is frequently responsible for invasive skeletal infections in children aged 3–36months. However, few outbreaks of invasive Kk infections in day care centers have been reported. The objective of the present study was to describe (a) the clinical and laboratory data recorded during an outbreak of invasive Kk skeletal infections, and (b) the management of the outbreak. MethodFour children from the same day care center were included in the study May and June 2019. We retrospectively analyzed the children's clinical presentation and their radiological and laboratory data. We also identified all the disease control measures taken in the day care center. ResultsWe observed cases of septic arthritis of the wrist (case #1), shoulder arthritis (case #2), knee arthritis (case #3) ans cervical spondylodiscitis (case #4). All cases presented with an oropharyngeal infection and concomitant fever prior to diagnosis of the skeletal infection. All cases were misdiagnosed at the initial presentation. The mean (range) age at diagnosis was 10.75months (9–12). The three patients with arthritis received surgical treatment. All patients received intravenous and then oral antibiotics. In cases 1 and 2, Kk was detected using real-time PCR and a ST25-rtxA1 clone was identified. The outcome was good in all four cases. Four other children in the day care center presented with scabies during this period and were treated with systemic ivermectin. The Regional Health Agency was informed, and all the parents of children attending the day care center received an information letter. The day care center was cleaned extensively. ConclusionOur results highlight the variety of features of invasive skeletal Kk infections in children and (given the high risk of transmission in day care centers) the importance of diagnosing cases as soon as possible.

Evaluating the Risks of Systemic Maternal Ivermectin Exposure During Pregnancy in Human and Vertebrate Animals: A Scoping Review.

Ivermectin is widely used for the treatment of neglected tropical diseases associated with adverse maternal and fetal outcomes when the infection complicates the pregnancy. However, the United States FDA classification and current distribution protocols limit ivermectin treatment in pregnant women because antepartum safety has not been well-established. We conducted a scoping review to address the question of what is known from both human and vertebrate animal studies about the safety of systemic ivermectin exposure during pregnancy. We searched PubMed for adverse outcomes related to systemic ivermectin exposure in human and vertebrate animal pregnancies, including English-language primary articles from 1900 - 2019. We identified 23 primary articles for evaluation, including 10 human studies and 13 vertebrate animal studies of interest. One prospective randomized, controlled trial investigating the safety of systemic ivermectin exposure during pregnancy and four retrospective human studies did not identify a significant association with adverse birth outcome metrics. Out of the three human case reports, two reported uncomplicated prenatal courses and one reported stillbirth and maternal death. A retrospective cross-sectional study concluded a positive association between onchocerciasis and spontaneous abortion, mitigated by ivermectin mass drug administration. While adverse pregnancy outcomes were observed at high doses in mice, rats, and rabbits, there was overall a lack of evidence to support concerns that therapeutic doses of ivermectin (0.2 mg/kg) cause adverse pregnancy outcomes. Further research is warranted to address safety concerns regarding the use of ivermectin in pregnant women in treating and preventing neglected helminth infections that threaten maternal-child health.

Ivermectin and permethrin for treating scabies.

Ivermectin and permethrin for treating scabies.

Management of Malignant Wound Myiasis with Ivermectin, Albendazole, and Clindamycin (Triple Therapy) in Advanced Head-and-Neck Cancer Patients: A Prospective Observational Study.

Introduction:Myiasis, tissue infestation by housefly larvae, is commonly found in malignant fungating wounds of cancer patients from climatic condition and lower socio-economic strata.Aim of study:It was aimed to study the effectiveness of systemic Ivermectin, Albendazole& Clindamycin (Triple Therapy) in reducing signs & symptoms associated with maggots in malignant head and neck wounds.Method:25 adult, advanced head and neck cancer patients presenting with maggots either from wound, oral cavity or nostril, with ECOG score 3 or less were enrolled in this study. Symptoms were assessed using Edmonton Symptom Assessment Scale (ESAS) and wound by Wound Assessment Tool – Hospice, at baseline and then Days 1, 3, 5, and 7. All patients received 3 days course of oral Ivermectin 12 mg per day, Albendazole 400 mg twice per day and Clindamycin 300 mg three times per day for 5 days along with Terpentine oil dressing. All patients received oral Morphine as per their pain score.Results:Mean age (yrs) and weight (Kg) were 42.15 ± 8.23 and 52.31 ± 5.18 respectively. 84% patients were male. Mean oral morphine dose was 100.38 mg. There was significant decrease in number of maggots from day 0 (77.28 ± 13.465) to day 1 (20.60 ± 7.263; 73.34% reduction) to day 3 (1.52 ± 2.104; 92.62% reduction). We found statistically significant improvement (P = <0.05) in scores of wound and all other related symptoms on days 1, 3, 5 & 7, except bleeding, edema, nausea, anxiety, appetite loss and feeling of wellbeing, which remained same on Day 1, but improved afterward. Side effects were self-limiting.Conclusion:Systemic treatment with Ivermectin, Albendazole and Clindamycin (Triple Therapy) enhances the removal of maggots, early recovery and relief from distress and associated symptoms.

The Treatment of Scabies.

Scabies is a contagious infestation transmitted by skin-to-skin contact and sometimes by contact with contaminated material. The scabies mite burrows into the skin, producing a papular rash and severe itch at typical sites of predilection. We systematically reviewed the literature to compare the efficacy of various anti-scabies agents, including a calculation of relative risks and confidence intervals. A literature search yielded 596 initial hits; after screening in accor-dance with the defined inclusion and exclusion criteria, 16 studies were selected for this review. Among topical treatments for scabies, permethrin was equally effective or more effective than crotamiton or benzyl benzoate. In a comparison of topical versus systemic treatment, topical permethrin and systemic ivermectin did not differ substantially in efficacy (7 comparative studies revealed no difference; one revealed a difference in favor of permethrin). Comparative trials of topical benzyl benzoate versus systemic ivermectin yielded inconsistent findings. Single and double administrations of ivermectin were similarly effective. In trials involving entire populations with a high prevalence of scabies, systemic ivermectin was found to be superior to topical permethrin. There are hardly any differences in efficacy between the available treatments for scabies. Single administrations of permethrin 5%, crotamiton 10%, and systemic ivermectin are all comparably effective. There are differences in the frequeny and ease of application as well as when eradicating scabies in populations with a high prevalence.

Pelodera strongyloides as a Cause of Severe Erythematous Dermatitis in 2 Guinea Pigs (Cavia porcellus)

In total, 2 pet guinea pigs (Cavia porcellus) that were 5 years old were presented with pruritus, erythema, alopecia, and crusting of the ventral abdomen. Skin scrapings revealed multiple nematode larvae, identified as Pelodera strongyloides based on morphologic characteristics. Treatment consisted of systemic ivermectin and fenbendazole in addition to topical benzoyl peroxide application. P. strongyloides is a free-living saprophytic nematode, which is ubiquitously present in any decaying organic material, such as soil or feed. The nematode is capable of invading mammalian skin, resulting in pruritic dermatitis. Diagnosis of the nematode induced skin disease is based on history, including husbandry, presence of a ventrally distributed dermatitis, and demonstration of larvae in skin scrapings. Dermal peloderosis cases have been reported in different animal species, including dogs, cattle, horses, sheep, and a laboratory housed guinea pig. This is the first description of P. strongyloides dermatitis in pet guinea pigs. P. strongyloides dermatitis should be considered as a differential diagnosis for alopecic and crusty skin lesions in guinea pigs.

Effect of Systemic Ivermectin on Epidermal Tunnel Size, Severe Asthetic Appearance of Skin, Haematological and Biochemical Inbalances Caused by Sarcoptes scabie var caprae in West African Dwarf Goats, in Ibadan, Nigeria

Effect of Systemic Ivermectin on Epidermal Tunnel Size, Severe Asthetic Appearance of Skin, Haematological and Biochemical Inbalances Caused by Sarcoptes scabie var caprae in West African Dwarf Goats, in Ibadan, Nigeria

Laboratory Evaluation of Oral Treatment of Rodents with Systemic Insecticides for Control of Bloodfeeding Sand Flies (Diptera: Psychodidae)

The purpose of this study was to evaluate the efficacy of oral treatment of rodents with diets containing the systemic insecticides ivermectin, abamectin, imidacloprid, or spinosad, to control bloodfeeding sand flies. We found that diets containing concentrations higher than 10 mg/kg abamectin were not palatable to rodents, and that a diet containing 10 mg/kg abamectin (a palatable concentration) did not cause 100% mortality of bloodfeeding sand flies. Treatment of rodents with imidacloprid was effective for less than 3 days post-treatment. Treatment of rodents with diets containing 20 mg/kg ivermectin or 5000 mg/kg spinosad caused 100% mortality of bloodfeeding sand flies for at least 1 week. The efficacy of ivermectin and spinosad also were not reduced when combined with the fluorescent tracer dye rhodamine B in a single diet. We also did not observe significant benefits by increasing the feeding period of the rodents from 3 to 6 or 9 days. We conclude that ivermectin and spinosad are effective as rodent systemic insecticides against bloodfeeding sand flies, and suggest that weekly treatment of wild rodent reservoirs of Leishmania major with bait containing one of these systemic insecticides could be a useful tool as part of a sand fly control program.

Clinical Treatment of Ocular Demodex folliculorum by Systemic Ivermectin

To report clinical outcomes of the treatment of ocular Demodex folliculorum with oral ivermectin. Noncomparative, interventional case series. Setting. Institutional. Study Population. Twenty-four eyes of 12 patients (3 male and 9 female; mean age ± standard deviation, 50.4 ± 21.0 years) with refractory posterior blepharitis with the presence of D. folliculorum in lash samples were enrolled in this study. Intervention. Patients were instructed to take 1 dose of oral ivermectin (200 μg/kg). All patients were instructed to repeat the treatment after 7 days. Main outcome measures. Tear meniscus height, Schirmer I test results, noninvasive tear film break-up time (BUT), quantification of the absolute number of D. folliculorum found in the lashes, and corneal fluorescein and rose bengal staining scores were obtained from all patients 1 day before and 28 days after treatment. Statistical improvement was observed in the absolute number of D. folliculorum found in the lashes after the treatment with oral ivermectin. Average values of Schirmer I test results and tear film break-up time improved statistically after the treatment of oral ivermectin. No statistical improvement was observed in average lacrimal meniscus height or value of corneal fluorescein and rose bengal staining after treatment with oral ivermectin. Ivermectin successfully reduced the number of D. folliculorum found in the lashes of patients with refractory blepharitis. Oral ivermectin may be very useful as a complement in the treatment of D. folliculorum infestation with ocular manifestation, especially in cases of unsuccessful treatment related to patient compliance.

Scabies Outbreak in an Intensive Care Unit with 1,659 Exposed Individuals—Key Factors for Controlling the Outbreak

To investigate a large outbreak of scabies in an intensive care unit of a university hospital and an affiliated rehabilitation center, and to establish effective control measures to prevent further transmission. Outbreak investigation. The intensive care unit of a 750-bed university hospital and an affiliated 92-bed rehabilitation center. All exposed individuals were screened by a senior staff dermatologist. Scabies was diagnosed on the basis of (1) identification of mites by skin scraping, (2) identification of mites by dermoscopy, or (3) clinical examination of patients without history of prior treatment for typical burrows. During a follow-up period of 6 months, the attack rate was calculated as the number of symptomatic individuals divided by the total number of exposed individuals. All exposed healthcare workers (HCWs) and their household members underwent preemptive treatment. Initially, the most effective registered drug in Switzerland (ie, topical lindane) was prescribed, but this prescription was switched to topical permethrin or systemic ivermectin as a result of the progression of the outbreak. Individuals with any signs or symptoms of scabies underwent dermatological examination. Within 7 months, 19 cases of scabies were diagnosed, 6 in children with a mean age of 3.1 years after exposure to the index patient with HIV and crusted scabies. A total of 1,640 exposed individuals underwent preemptive treatment. The highest attack rate of 26%-32% was observed among HCWs involved in the care of the index patient. A too-restricted definition of individuals at risk, noncompliance with treatment, and the limited effectiveness of lindane likely led to treatment failure, relapse, and reinfestation within families. Crusted scabies resulted in high attack rates among HCWs and household contacts. Timely institution of hygienic precautions with close monitoring and widespread, simultaneous scabicide treatment of all exposed individuals are essential for control of an outbreak.

Fallberichte

A 38 year old woman from Dresden presented in September 2002, about four weeks after the Elbe River flooding with signs of cutaneous larva migrans on the back of her hand. There was no history of travel to tropical or subtropical regions in the last few years. Cryotherapy as well as systemic ivermectin (Stromectol) therapy were not successful in stopping progress of the lesions. Combination therapy with systemic ivermectin and topical tiabendazole (Lombristop) induced full remission. Cutaneous larva migrans normally occurs in German patients only after recent visits to tropical or subtropical regions. In our patient, however, it was most likely due to the unusual climatic conditions in the summer of 2002 in the Elbe region: Heavy rainfalls and inundation by regional rivers soaked the ground, followed by a period of unusually hot and sunny weather.

Current treatments for scabies.

Scabies is a frequent interhuman ectoparasitic infection. Several treatments are available worldwide. There are local treatments: synthetic pyrethrins, benzyl benzoate, lindane, crotamiton. Recently a few studies were published concerning ivermectin, systemic antiparasitic agent use in onchocercosis treatment. We reviewed the literature with an evidence-based medicine method. We attempt to answer two questions in particular: what is the treatment of choice for common scabies in a patient otherwise in good health? What is the role of systemic ivermectin? We also report specific situations. Among local treatments, studies are heterogeneous according to products, countries, group of treated patients, with or without contact subjects, and the method of treatment application. There are very few high proof-level controlled studies. In France, a combination of benzyl benzoate 10% and sulfiram 2% is used most, according to professional consensus. The most studied product is the cream permethrin 5%, available in the USA and UK. Its efficacy seems slightly superior to lindane and less toxic. It is more efficient than crotamiton. There is no study comparing benzyl benzoate and permethrin. Concerning systemic ivermectin, five controlled studies showed its efficiency in common scabies. But its relative efficiency over local treatment has not been established. A few open studies showed its efficacy in institutional epidemic, profuse scabies and in HIV-positive patients. Local treatment of choice in common scabies remains to be determined among the four principal molecules. There is no study comparing permethrin or esdepallethrin to benzyl benzoate. In what cases should we prescribe crotamiton or lindane? Indication of ivermectin seems proved in common scabies and probably for HIV-positive patients. It remains to be determined if it should be prescribed in the first instance, be double or triple, be associated or not with local treatment. In case of keratotic scabies, ivermectin seems interesting with two applications within 1 week, and should be associated with local treatment (duration remains to be defined). Ivermectin is probably useful in institutional epidemic, and therapeutic attitude remains to be defined. Ivermectin seems to have little or no risk. Treatment must be adapted case-by-case, according to feasibility. It is still important to treat contacts, and modality of this treatment remains to be specified.

Management of endemic outbreaks of scabies with allethrin, permethrin, and ivermectin.

At three residences for the elderly, recurrent scabies infestations became out of control. Due to the failure of repeated, nonsynchronized therapeutic efforts with conventional external anti-scabies treatments, an eradication program had to be developed. We describe a protocol for the management of outbreaks of scabies. According to the clinical examination and microscopically identified mites, all individuals of the population (IOP: patients, staff, and family members) were divided into two groups: (a) healthy and infested IOP; and (b) cases with crusted scabies. The first group was treated simultaneously once with external scabicides (allethrin or permethrin). All others were hospitalized and treated either with systemic ivermectin or with the latter in combination with permethrin. In 252 IOP living in three residences for the elderly, clinical signs of scabies were reported in 91.5%, 78.5%, and 15.4% of the patients (age 55-97 years; mean, 80.5 years), 54.1%, 32.9%, and 16.6% of staff members, and in 7%, 3%, and 0% of family members. The infested IOP showed crusted scabies (index cases) in 5.3%, 5.0%, and 1.7%, common scabies in 43.1%, 36.7%, and 7.1%, and postscabiotic dermatitis in 10.3%, 7.6%, and 3.5%. In 99.2% of the synchronously treated IOP in group (a) (n = 240), the conventional treatment with permethrin cream 5% or allethrin spray was effective. Group (b) (n=12) received ivermectin (12 mg) once (n=5) or twice (n= 7) after an interval of 8 days. One index case received permethrin three times. Outbreaks of scabies in populations of elderly people require special management for disease control. Synchronous treatment with external permethrin cream 5% or allethrin spray, including all IOP once, and close control offers a time-saving, cheap, and reliable method. Crusted scabies should be treated by oral administration of ivermectin once or twice after an interval of 8 days. Additional applications of permethrin and mechanical clearing of hyperkeratotic subungual areas shorten the course.

Sensitization to dust mites in cats with Otodectes cynotis infestation.

Sensitization to the dust mites was demonstrated by an intradermal (ID) skin test in 33 of 55 cats with Otodectes cynotis infestation. Positive ID test reactions to Dermatophagoides farinae were noticed in 32 (58.2%), to Dermatophagoides pteronyssinus in 29 (52.7%) and to Acarus siro in seven (12.7%) cats. The presence (P = 0.03) and duration (P = 0.04) of pruritus were positively associated with the ID test results. All the cats had a complete response to systemic ivermectin therapy, although three of them became reinfested as soon as they were in contact with other cats. The ID test was negative in 25 cats that had reacted positive previously, when the test was repeated 3-6 months after the acaricidal treatment. During that time there was no evidence of concurrent ectoparasitic infestation. The remaining eight cats were re-infested by O. cynotis or lost to follow-up.

Experimental infection of dogs with the nasal mite Pneumonyssoides caninum

A successful experimental transmission of the canine nasal mite, Pneumonyssoides caninum, is described. Some 11 weeks after repeated systemic ivermectin treatment, four Beagles were inoculated via the right nostril with 20 P. caninum mites of different sexes and life stages, obtained at the necropsy of an infected dog. The inoculated dogs and a matching uninoculated control were observed for clinical signs for 14 weeks and then euthanised. Vague upper respiratory signs and a transient minor increase in the number of eosinophils in peripheral blood were recorded in the inoculated dogs. At necropsy 4–12 P. caninum mites were found in the nasal cavities and sinuses of the inoculated dogs, but none in the control. In three out of the four infected dogs mites were found in both the right and left nasal cavities and sinuses of the skull. Since in no case more mites than the number used for inoculation were detected it is not clear if the mites managed to reproduce in the dogs. Inflammatory lesions were seen most consistently in the olfactory mucosa, respiratory mucosa and tonsils, and growth of opportunistic bacteria was observed in the tonsils of the infected dogs. The inflammatory lesions seen in the olfactory mucosa may explain why dogs infected with P. caninum sometimes appear to suffer from impaired scenting ability.