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Background: With widespread insecticide resistance in mosquito vectors, there is a pressing need to evaluate alternatives with different modes of action. Blood containing the antihelminthic drug ivermectin has been shown to have lethal and sub-lethal effects on mosquitoes. Almost all work to date has been on Anopheles spp., but impacts on other anthropophagic vectors could provide new options for their control, or additional value to anti-malarial ivermectin programmes., Methods: Using dose-response assays, we evaluated the effects of ivermectin delivered by membrane feeding on daily mortality (up to 14 days post-blood feed) and fecundity of an Indian strain of Aedes aegypti., Results: The 7-day lethal concentration of ivermectin required to kill 50% of adult mosquitoes was calculated to be 178.6 ng/ml (95% confidence intervals 142.3-218.4) for Ae. aegypti, which is much higher than that recorded for Anopheles spp. in any previous study. In addition, significant effects on fecundity and egg hatch rates were only recorded at high ivermectin concentrations (≥ 250 ng/ul)., Conclusion: Our results suggest that levels of ivermectin present in human blood at current dosing regimes in mass drug administration campaigns, or even those in a recent higher-dose anti-malaria trial, are unlikely to have a substantial impact on Ae. aegypti. Moreover, owing to the strong anthropophagy of Ae. aegypti, delivery of higher levels of ivermectin in livestock blood is also unlikely to be an effective option for its control. However, other potential toxic impacts of ivermectin metabolites, accumulation in tissues, sublethal effects on behaviour, or antiviral action might increase the efficacy of ivermectin against Ae. aegypti and the arboviral diseases it transmits, and require further investigation.

In an effort to curb the global pandemic due to coronavirus, the scientific community is exploring various treatment strategies with a special emphasis on drug repurposing. Ivermectin, an anti-helminthic drug is also being proposed for treatment and prevention of COVID-19. Ivermectin has demonstrated broad spectrum antiviral activity against both DNA and RNA viruses. Due to its potential to interfere with transport of SARS-CoV-2 nucleocapsid protein to nucleus, it is being proposed to have antiviral activity against this virus as well which has been confirmed in an in-vitro study. However, in-vitro to in-vivo extrapolation studies indicate an inability to achieve the desired IC50 levels of ivermectin after oral administration of doses up to 10 times higher than the approved anti-helminthic dose. In a modelling simulation study, drug accumulation in the lungs was noticed at levels having potential antiviral activity. It is hypothesised that inhaled formulation of ivermectin may be effective against SARS-CoV-2. Therefore, ivermectin administered via inhalational route needs to be explored for potential beneficial role in COVID-19 in preclinical and clinical studies. We also hypothesise the possibility of drug having anti-inflammatory action in coronavirus associated severe respiratory illness based on few in-vitro and in-vivo reports which however needs to be confirmed clinically., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Scabies is globally ubiquitous and is a significant health issue for institutions, the economically disenfranchised, resource-poor areas, and for those with weakened immune systems. Topicals are usually effective, but are cumbersome and expensive to use in large populations and for those nonadherent to topicals. Oral ivermectin became available in Canada for the off-label treatment of scabies in the fall 2018., Objectives: To review the diagnosis and management of scabies. Dose schedules and concomitant management measures are outlined for scabies simplex and for crusted scabies. Ivermectin use is outlined., Methods: Medline, colleague discussions, practice review, and experience from managing scabies in institutions., Results: Oral ivermectin is safe, easier to use, cheaper, more effective, and more economical than topicals in widespread institutional scabies, for those nonadherent to topicals, and in crusted scabies., Conclusions: Oral ivermectin is the treatment of choice in large populations, the nonadherent, and for crusted scabies. Oral ivermectin is produced by Merck Canada as Stromectol 3 mg. The treatment dose for noncrusted scabies is 200 µg/kg, taken in a single dose with food. For example, 15 mg (5 tablets) for a 70 kg person. Retreat in 10-14 days to enhance effectiveness, and perhaps to reduce scabicide resistance.

The difficult experience of treating scabies in an elderly hospital reaffirmed my determination and responsibilities as a pharmacist. In 2000, there was no effective treatment for scabies in Japan. With the Japan Pharmaceutical Association as well as the Japanese Dermatological Association, the indication of ivermectin which is the intestinal fecal nematode was expanded for scabies. Since it was found that the administration of ivermectin through a tube to patients who could not take it orally had a dose loss of 50% depending on the injection method, an appropriate administration method was proposed. However, the oral administration of ivermectin has side effects including systemic liver damage, and external preparations require labor for systemic application, and recurrence from unapplied areas is also a problem. Therefore, we devised a whole-body bathing, in which patients are immersed in a fluid that contains ivermectin. The repeated ivermectin bathing three times a week cured scabies and has no problematic side effects in the clinical trial, suggesting that this method is a safer treatment. Next, in Okinawa, phenothrin-resistant head lice infestation was prevalent, and no medical drug for this infestation is available in Japan yet. Hence, to address this situation, we conducted a clinical trial to investigate the efficacy and safety of a combination regimen of 5% topical phenothrin and the unapproved 0.5% topical ivermectin. Consequently, 92% and 100% effectiveness were obtained in Okinawa and Tsukuba, respectively. As a result, we were able to conduct research aimed to maximize the safety and effectiveness of ivermectin in Japan.

There is only limited scientific literature on trial methodology, trial procedures and mitigation strategies to overcome challenges faced during clinical research taking place in resource constrained healthcare environments. Organisational, cultural, infrastructural and ethical challenges may vary between settings although conduct of clinical trials for the same disease (in our case soil-transmitted helminth (STH) infections) share similar risks for implementation. We use the example of a phase III randomised controlled trial, conducted between 2018 and 2020 in Côte d'Ivoire, Lao PDR and Pemba Island (Tanzania), to share challenges faced and mitigation strategies to guide future planning of studies in similar settings. We describe the planning, screening, enrolment and implementation phases in each of the three settings. Our findings indicate that involvement of local staff and close collaboration are essential factors for successful trial preparation and implementation. A strategic plan adapted to each setting with a distinct focus on community engagement and workforce is crucial to proceed efficiently. Mutual trust between the trial population and the trial team is of utmost importance and allows for early reaction and adaption to emerging issues., (© 2021 Elsevier Ltd. All rights reserved.)

Ivermectin is a broad-spectrum antiparasitic agent used for the treatment and control of neglected tropical diseases. In Australia, ivermectin is primarily used for scabies and is licensed in children aged ≥5 years weighing >15 kg. However, young children, aged <5 years, are particularly vulnerable to scabies and its secondary complications. Therefore, this study aimed to determine an appropriate ivermectin dose for children aged 2 to 4 years and weighing ≤15 kg. We conducted a prospective, pharmacokinetic study of ivermectin in Indigenous Australian children aged between 5 and 15 years and weighing >15 kg. Doses of 200 μg/kg rounded to the nearest whole or half 3 mg tablet were given to children with scabies and ivermectin concentrations determined at two time points after dosing. A population pharmacokinetic model was developed using non-linear mixed effects modelling. A separate covariate database of children aged 2 to 4 years and weighing <15 kg was used to generate 1000 virtual patients and simulate the dose required to achieve equivalent drug exposure in young children as those aged ≥5 years. Overall, 26 children who had 48 ivermectin concentrations determined were included, 11 (42%) were male, the median age was 10.9 years and median body weight 37.6 kg. The final model was a two-compartment model with first-order absorption and linear elimination. For simulated children aged 2 to 4 years, a dose of 3 mg in children weighing 10-15 kg produced similar drug exposures to those >5 years. The median simulated area under the concentration-time curve was 976 μg∙h/L. Using modelling, we have identified a dosing strategy for ivermectin in children aged 2 to 4 years and weighing less than 15 kg that can be prospectively evaluated for safety and efficacy., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: AG has attended the MSD Asia Pacific forum. No other authors have competing interests.

This study describes the first known occurrence and treatment of enzootic cutaneous myiasis by Dermatobia hominis in a herd of sambar deer (Rusa unicolor). Sambar deer are clinically affected by enzootic cutaneous myiasis during the spring and summer in Rio de Janeiro, Brazil. Through direct inspection and clinicopathological evaluation in the herd with 80 R. unicolor, it was observed that infestation by D. hominis caused 100% morbidity. At histological exam, skin had eosinophilic and granulomatous chronic active severe necrohemorrhagic dermatitis associated with botfly and moderate surrounding fibroplasia. The systemic treatment with oral ivermectin at 0.08% was effective in 93.7% of deer with enzootic cutaneous myiasis after fourteen days. After treatment, the skin deer had eosinophilic and granulomatous chronic severe dermatitis associated with degenerated botfly and severe fibroplasia. Notable differences in leukocyte profile were observed between groups pre- and post-treatment. Decrease of relative values of neutrophils and eosinophils were significant in the treated deer group. An increase of relative values of monocytes was also confirmed in the treated group. Sambar deer was the only species affected by D. hominis, even though several other wild herbivores were kept in the same area. More studies are needed to elucidate the susceptibility of R. unicolor to D. hominis cutaneous infestations.

SARS-CoV-2 utilizes the IMPα/β1 heterodimer to enter host cell nuclei after gaining cellular access through the ACE2 receptor. Ivermectin has shown antiviral activity by inhibiting the formation of the importin-α (IMPα) and IMPβ1 subunits as well as dissociating the IMPα/β1 heterodimer and has in vitro efficacy against SARS-CoV-2. Plasma and lung ivermectin concentrations vs. time profiles in cattle were used to determine the apparent plasma to lung tissue partition coefficient of ivermectin. This coefficient, together with a simulated geometric mean plasma profile of ivermectin from a published population pharmacokinetic model, was utilized to develop a minimal physiologically-based pharmacokinetic (mPBPK) model. The mPBPK model accurately described the simulated ivermectin plasma concentration profile in humans. The mPBPK model was also used to simulate human lung exposure to ivermectin after 12, 30, and 120 mg oral doses. The simulated ivermectin lung exposures reached a maximum concentration of 772 ng/mL, far less than the estimated 1750 ng/mL IC 50 reported for ivermectin against SARS-CoV-2 in vitro. Further studies of ivermectin either reformulated for inhaled delivery or in combination with other antivirals with differing mechanisms of action is needed to assess its therapeutic potential., (Copyright © 2020. Published by Elsevier Inc.)

This study aims to evaluate the influence of the phase behavior of microemulsions in the transdermal administration ("spot-on") of ivermectin, an antiparasitic drug widely used in the treatment of endoparasites and ectoparasites in dogs. In this regard, pseudoternary phase diagrams composed of water (aqueous phase), isopropyl myristate (oil phase), tween 80 (surfactant) and labrasol (cosurfactant) were obtained in a different surfactant: cosurfactant (S:CS) ratios. S:CS in 1:3 ratio presented a larger region of microemulsion formation and three microemulsions were selected from it and characterized. Subsequently, in vitro permeation and retention studies were conducted using canine skin as membrane. SAXS, rheology and conductivity data were employed to confirm the phase behavior of the microemulsions (w/o, bicontinuous or o/w). The cutaneous permeation and retention tests showed that the w/o microemulsion, followed by bicontinuous microemulsion, resulted in a higher amount of drug permeated through canine skin, suggesting better transdermal permeation. On the other hand, o/w microemulsion resulted in a higher amount of drug accumulated into the skin, suggesting better topical activity. Thus, it can be concluded that phase behavior of microemulsions influenced the drug permeation in the canine skin differently from other animal models. Microemulsions, especially w/o and bicontinuous, can be promising vehicles regarding the transdermal delivery of ivermectin., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The Global Programme to Eliminate Lymphatic Filariasis has made considerable progress but is experiencing challenges in meeting targets in some countries. Recent World Health Organization guidelines have recommended two rounds of triple-drug therapy with ivermectin, diethylcarbamazine (DEC), and albendazole (IDA), in areas where mass drug administration (MDA) results with two drugs (DEC and albendazole) have been suboptimal, as is the case in Samoa. In August 2018, Samoa was the first country in the world to implement countrywide triple-drug MDA. This paper aims to describe Samoa's experience with program coverage and adverse events (AEs) in the first round of triple-drug MDA. We conducted a large cross-sectional community survey to assess MDA awareness, reach, compliance, coverage and AEs in September/October 2018, 7-11 weeks after the first round of triple-drug MDA. In our sample of 4420 people aged ≥2 years (2.2% of the population), age-adjusted estimates indicated that 89.0% of the eligible population were offered MDA, 83.9% of the eligible population took MDA (program coverage), and 80.2% of the total population took MDA (epidemiological coverage). Overall, 83.8% (2986/3563) reported that they did not feel unwell at all after taking MDA. Mild AEs (feeling unwell but able to do normal everyday things) were reported by 13.3% (476/3563) and moderate or severe AEs (feeling unwell and being unable to do normal everyday activities such as going to work or school) by 2.9% (103/3563) of participants. This study following the 2018 triple-drug MDA in Samoa demonstrated a high reported program awareness and reach of 90.8% and 89.0%, respectively. Age-adjusted program coverage of 83.9% of the total population showed that MDA was well accepted and well tolerated by the community., Competing Interests: The authors have declared that no competing interests exist.

The aims of this study were to evaluate the efficacy of two injectable formulations of doramectin (DRM) against Psoroptes ovis in sheep infested under controlled experimental conditions and to characterize the DRM plasma disposition kinetics in the infested animals. To this end, sheep were experimentally infested with a P. ovis strain from a farm with a history of treatment failure, and then treated either with DRM 1% (traditional preparation) on days 0 and 7 or with DRM 3.15% (long-acting formulation) on day 0. The efficacy of each treatment was calculated by counting live mites in skin scrapings. Plasma samples were obtained from each animal and DRM concentrations were measured by HPLC. After the two doses of DRM 1%, the maximum efficacy (98.8%) was reached on day 28, whereas after the single dose of DRM 3.15%, the maximum efficacy (100%) was reached on day 35 and ratified on day 42. The long-acting formulation allowed obtaining higher exposure and more sustained concentrations of DRM than the traditional preparation. Although both DRM formulations studied were effective according to international protocols, they did not reach 100% effectiveness in the time required for approved pharmaceutical products against sheep scab, according to Argentine regulations., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Demodex folliculorum is a mite that commonly inhabits the pilosebaceous units of facial skin, particularly in a perioral and periorbital distribution. While typically an incidental and asymptomatic parasite, Demodex spp. are proposed to contribute to the pathogenesis of facial folliculitis, chronic blepharitis and papulopustular rosacea. Reports of demodicosis in anatomic locations other than the face are exceedingly rare. Here we report a 36-year-old woman with symptomatic Demodex spp. infestation of Fordyce spots of the labia minora. She was referred to dermatology after a 9-month history of tender red bumps on the vulva that would arise and drain over a 24 to 72 hours period, several times per week. Physical examination revealed erythema of the labia minora and introitus with a 4 mm, pink, dome-shaped soft papule on the left labium minus. Wet mount, microbiologic cultures and sexually transmitted infection (STI) screenings were unremarkable. Histopathologic examination revealed a well-circumscribed nodule of suppurative granulomatous inflammation arising in a background of mucosa with Fordyce spots, the majority of which were infiltrated by Demodex spp. Treatment with oral ivermectin and topical metronidazole cream resulted in a symptom-free period of 22 months. This case represents an unusual presentation of symptomatic Demodex infestation., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Introduction: Moxidectin is a milbemycin endectocide recently approved for the treatment of human onchocerciasis. Onchocerciasis, earmarked for elimination of transmission, is a filarial infection endemic in Africa, Yemen, and the Amazonian focus straddling Venezuela and Brazil. Concerns over whether the predominant treatment strategy (yearly mass drug administration (MDA) of ivermectin) is sufficient to achieve elimination in all endemic foci have refocussed attention upon alternative treatments. Moxidectin's stronger and longer microfilarial suppression compared to ivermectin in both phase II and III clinical trials indicates its potential as a novel powerful drug for onchocerciasis elimination., Areas Covered: This work summarizes the chemistry and pharmacology of moxidectin, reviews the phase II and III clinical trials evidence on tolerability, safety, and efficacy of moxidectin versus ivermectin, and discusses the implications of moxidectin's current regulatory status., Expert Opinion: Moxidectin's superior clinical performance has the potential to substantially reduce times to elimination compared to ivermectin. If donated, moxidectin could mitigate the additional programmatic costs of biannual ivermectin distribution because, unlike other alternatives, it can use the existing community-directed treatment infrastructure. A pediatric indication (for children <12 years) and determination of its usefulness in onchocerciasis-loiasis co-endemic areas will greatly help fulfill the potential of moxidectin for the treatment and elimination of onchocerciasis.

Background: Ivermectin-based preventive chemotherapy (PC) is distributed annually to all at-risk populations eligible for ivermectin treatment to control and/or eliminate onchocerciasis. Information on the impact of mass ivermectin administration on onchocerciasis transmission is scanty, and it is tricky to appreciate the progress towards elimination and engage corrective measures. To fill that gap in the Centre Region in Cameroon, the current onchocerciasis endemicity level in the Ndikinimeki Health District after about two decades of mass treatments was assessed., Methods: A cluster-based cross-sectional survey was carried out in the Ndikinimeki Health District and all volunteers aged ≥ 5 years were (i) interviewed on their compliance to ivermectin over the past five years and (ii) underwent clinical (nodule palpation and visual search for onchocercal lesions) and parasitological examinations (skin snip) for onchocerciasis., Results: The overall Onchocerca volvulus prevalence was 7.0% (95% CI: 5.2-9.3%). The prevalence of the disease was significantly higher in the communities Kiboum 1 and Kiboum 2 compared to the other communities (highest prevalence in Makénéné Town Water: 8.5%; 95% CI: 2.3-20.4%) (χ 2 = 51.314, df = 11, P = 0.0001). The proportion of systematic non-compliers to ivermectin was 23.3% (95% CI: 19.9-27.1%) among individuals interviewed. In the sentinel sites (Kiboum communities), onchocerciasis prevalence decreased from 95.2% (95% CI: 88.3-98.1%) to 23.7% (95% CI: 14.7-36.0%)., Conclusions: This study has revealed that the Ndikinimeki Health District is hypo-endemic for onchocerciasis after about two decades of preventive chemotherapy. However, transmission is ongoing, with potential hotspots in the Kiboum 1 and Kiboum 2 communities, which are known as first-line communities (closest to the breeding sites of the vector). Alternative or complementary strategies to annual ivermectin appear compulsory to accelerate the momentum towards onchocerciasis elimination.

The objective was to investigate the effect of injectable eprinomectin on milk yield and quality of dairy ewes naturally infected with gastrointestinal nematodes when grazing in communal pastures. Onehundred and fifty (150) clinically healthy adult lactating ewes, equally selected from 3 farms, were included in the study. On day -7, the ewes on each farm were randomly allocated into 2 equal groups of 25 animals (n=50): Control group (C) and Treated group (T). On day 0, ewes in group T were given a single subcutaneous injection of eprinomectin at a dose rate of 0.2 mg/kg bodyweight. Ewes in group C were left untreated during the whole experiment. Ewes in group T with a fecal egg count (FEC) >300 eggs per g on day +60 were treated again. Fecal samples were individually collected on days -7, 0, +30, +60, +90, +120 for FEC estimations and coprocultures. On days -7, 0, +30, +60 and +90, individual milk yield (MY) was recorded using ICAR approved volumetric milk meters. Energy corrected milk yield (ECMY) for 6% fat was also calculated. Moreover, individual milk samples were collected on each day for determination of chemical composition [fat (F%), protein (P%) and lactose (L%) content] and somatic cell counts (SCC). On each day, individual fat and protein yield (FY and PY, respectively) were calculated. Total lactation MY, total ECMY, total FY and total PY were computed. The most prevalent parasite at pre-treatment and post-treatment days was Haemonchus spp. The overall efficacy on days +30 and +90 was 97.27 % and 98.80 %, respectively. In two out of the three farms, 80 % and 91.3 % of T ewes received a second treatment on day +60, due to high parasitic burden. Treatment had a significant effect (P=0.033) on MY with an average benefit of 8%. No significant effects of treatment were observed on the other parameters, although values were constantly numerically higher for treated ewes compared to control ones. In this field trial, injectable eprinomectin had a high overall efficacy and a beneficial effect on daily milk yield., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Rosacea is a chronic skin condition characterized by primary and secondary manifestations affecting the centrofacial skin. The primary diagnostic phenotypes for rosacea are fixed centrofacial erythema with periodic intensification, and phymatous changes. Major phenotypes, including papules and pustules, flushing, telangiectasia, and ocular manifestations, may occur concomitantly or independently with the diagnostic features. The phenotypes of rosacea patients may evolve between subtypes and may require multiple treatments concurrently to be effectively managed. We report the proceedings of a roundtable discussion among 3 dermatologists experienced in the treatment of rosacea and present examples of rosacea treatment strategies that target multiple rosacea symptoms presenting in individual patients., Methods: Three hypothetical cases describing patients representative of those commonly seen by practicing dermatologists were developed. A roundtable discussion was held to discuss overall and specific strategies for treating rosacea based on the cases., Results/discussion: With few exceptions, the dermatologists recommended combination therapy targeting each manifestation of rosacea for each case. These recommendations are in agreement with the current American Acne and Rosacea Society treatment guidelines for rosacea and are supported by several studies demonstrating beneficial results from combining rosacea treatments., Conclusions: Rosacea is an evolving condition; care should take into account all clinical signs and symptoms of rosacea that are present in an individual patient, understanding that symptoms may change over time, and utilize combination therapy when applicable to target all rosacea symptoms. J Drugs Dermatol. 2020;19(10): 929-934. doi:10.36849/JDD.2020.5367.

Caly et al. 1 reported that ivermectin inhibited severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in vitro for up to 48 hours using ivermectin at 5 μM. The concentration resulting in 50% inhibition (IC 50 ; 2 µM) was > 35× higher than the maximum plasma concentration (C max ) after oral administration of the approved dose of ivermectin when given fasted. Simulations were conducted using an available population pharmacokinetic model to predict total (bound and unbound) and unbound plasma concentration-time profiles after a single and repeat fasted administration of the approved dose of ivermectin (200 μg/kg), 60 mg, and 120 mg. Plasma total C max was determined and then multiplied by the lung:plasma ratio reported in cattle to predict the lung C max after administration of each single dose. Plasma ivermectin concentrations of total (bound and unbound) and unbound concentrations do not reach the IC 50 , even for a dose level 10× higher than the approved dose. Even with the high lung:plasma ratio, ivermectin is unlikely to reach the IC 50 in the lungs after single oral administration of the approved dose (predicted lung: 0.0873 µM) or at doses 10× higher that the approved dose administered orally (predicted lung: 0.820 µM). In summary, the likelihood of a successful clinical trial using the approved dose of ivermectin is low. Combination therapy should be evaluated in vitro. Repurposing drugs for use in coronavirus disease 2019 (COVID-19) treatment is an ideal strategy but is only feasible when product safety has been established and experiments of repurposed drugs are conducted at clinically relevant concentrations., (© 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Nitric oxide (NO) is a mediator and biomarker of pro- and anti-inflammatory processes. Excessive levels of NO for long periods have been associated with inflammation and tissue damage. The metabolism and synthesis of NO is usually measured indirectly, as metabolites and enzymes involved in reactions, often as the nitrite/nitrate (NOx) level. The aim of the present study was to measure the NOx levels in vital organs of juvenile silver catfish (Rhamdia quelen) exposed to various levels of eprinomectin in the water. The fish were exposed for 24 and 48 h to start concentration (0 h) of eprinomectin in water (0.0, 1.12, 1.80, and 3.97 μg/L). The eprinomectin concentrations in water were lower at 24 h (0.0, 0.85, 1.14, and 1.15 μg/L) and 48 h (0.0, 0.39, 0.69, and 1.28 μg/L), due to the process of eprinomectin metabolization. Subsequently, the fish were left for 48 h of recovery in eprinomectin-free water. NO levels were measured indirectly, as NOx levels in brain, liver, and gill tissue. Within 24 h of exposure, there was no significant increase in NOx levels in the organs evaluated at any of the concentrations tested. However, increases in NOx levels did occur at 48 h of exposure in all organs, particularly at the two highest concentrations of eprinomectin (1.80 and 3.97 μg/L). The transfer of fish to eprinomectin-free water did not result in reversal of NOx levels after 48 h of recovery, especially in fish that had been exposed to the two highest concentrations in the brain and liver tissues, and for the highest concentration in the gills. We conclude that silver catfish exposed to eprinomectin for up to 48 h present possible cerebral, hepatic, and branchial inflammatory process associated with increased tissue NOx levels, and that recovery for 48 h in water without antiparasitic is insufficient for the fish to recover from the poisoning.

Mass Drug Administration (MDA) programs to eliminate Lymphatic Filariasis (LF) in western Africa use the anthelminthics ivermectin plus albendazole. These drugs have the potential to impact also Soil-Transmitted Helminth (STH) infections, since the drugs have a broad range of anthelminthic activity. Integration of preventive chemotherapy efforts for LF, onchocerciasis and STH is recommended by the World Health Organization (WHO) in order to avoid duplication of MDA and to reduce costs. The objective of the current study was to determine whether five semi-annual rounds of community-wide MDA to eliminate LF and onchocerciasis have a greater impact on STH than three annual rounds of MDA with similar compliance. The effects of MDA using ivermectin (IVM, 0.2 mg/kg) combined with albendazole (ALB, 400 mg) on the prevalence and intensity of hookworm infection were evaluated in the Abengourou (annual MDA) and Akoupé (semi-annual MDA) health Districts in eastern Côte d'Ivoire from 2014 to 2017. A cross-sectional approach was used together with mixed logistic regression, and mixed linear models. Subjects were tested for STH using the Kato-Katz technique before the first round of MDA and 12, 24, and 36 months after the first round of MDA. The mean self-reported MDA compliance assessed during the survey was 65%, and no difference was observed between treatment areas. These results were confirmed by an independent coverage survey as recommended by WHO. Hookworm was the most prevalent STH species in both areas (23.9% vs 12.4%) and the prevalence of other STH species was less than 1%. The crude prevalence of hookworm dropped significantly, from 23.9% to 5.5% (p <0.001, 77% reduction) in the annual MDA treatment area and from 12.4% to 1.9% (p <0.001, 85% reduction) in the semi-annual treatment area. The average intensity of hookworm infection decreased in the annual MDA area (406.2 epg to 118.3 epg), but not in the semi-annual MDA area (804.9 epg to 875.0 epg). Moderate and heavy infections (1% and 1.3% at baseline) were reduced to 0% and 0.4% in the annual and semi-annual treatment areas, respectively. Using a mixed logistic regression model, and after adjusting for baseline prevalence, only the year 2 re-examination showed a difference in prevalence between treatments (OR: 2.26 [95% CI: 1.03, 4.98], p = 0.043). Analysis of intensity of hookworm infection indicated also that treatment differences varied by follow-up visit. In conclusion twelve months after the last treatment cycle, three annual and five semi-annual rounds of community-wide MDA with the combination of IVM and ALB showed strong, but similar impact on hookworm prevalence and intensity in eastern Côte d'Ivoire. Therefore, an annual MDA regimen seems to be an efficient strategy to control hookworm infection in endemic areas with low and moderate infection prevalence. Trial registration: The study was registered at ClinicalTrial.gov under the number NTC02032043., Competing Interests: The authors have declared that no competing interests exist.

We compared the pharmacokinetics of ivermectin premix and ivermectin microspheres in pigs after single and multiple administration regimes. In the single-dose experiments, 24 piglets were randomly divided into three groups and given ivermectin at 0.3 mg/kg using (a) 1.0% ivermectin administered subcutaneously, (b) 0.25% ivermectin premix orally, and (c) 0.25% ivermectin microspheres orally. In the multiple-dose experiment, 6 pigs in two equal groups received ivermectin premix and microspheres orally at 0.3 mg/kg for 7 consecutive days to monitor the valley plasma levels. The plasma samples were detected by fluorescence high-performance liquid chromatography, and concentration-time data were fitted to a noncompartmental model. After oral administration of ivermectin microspheres at a single dose, the elimination rate constant (Kel), the half-life (t 1/2 ), the peak time (T max ), the mean residence time (MRT), and the peak concentration (C max ) were 0.012 ± 0.0031/hr, 59.94 ± 20.18 hr, 9.50 ± 0.93 hr, 55.96 ± 11.40 hr, and 37.75 ± 3.45 ng/ml, respectively. The C max of microspheres was not statistically different (p > .05) compared with that of premix groups (39.81 ± 5.83 ng/ml). Moreover, the AUC of the microcapsule groups was increased from 1,129.76 ± 245.62 to 1,607.33 ± 343.35 hr ng/ml compared with the premix groups, and the relative bioavailability increased by an average of 17.53% after oral administration with ivermectin microspheres. Multiple-dose administration also indicated pigs fed with ivermectin microspheres can get a higher minimum steady-state concentration and a longer maintenance time than ivermectin premix., (© 2020 John Wiley & Sons Ltd.)

Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor and cognitive deficits, the result of dopamine (DA)-depletion within the basal ganglia. Currently, DA replacement therapy in the form of Sinemet (L-DOPA plus Carbidopa) provides symptomatic motor benefits and remains the "gold standard" for treatment. Several pharmacological approaches can enhance DA neurotransmission including the administration of DA receptor agonists, the inhibition of DA metabolism, and enhancing pre-synaptic DA release. DA neurotransmission is regulated by several receptor subtypes including signaling through the purinergic system. P2 × 4 receptors (P2 × 4Rs) are a class of cation-permeable ligand-gated ion channels activated by the synaptic release of extracellular adenosine 5'-triphosphate (ATP). P2 × 4Rs are expressed throughout the central nervous system including the dopaminergic circuitry of the substantia nigra, basal ganglia, and related reward networks. Previous studies have demonstrated that P2 × 4Rs can modulate several DA-dependent characteristics including motor, cognitive, and reward behaviors. Ivermectin (IVM) and moxidectin (MOX) are two macrocyclic lactones that can potentiate P2 × 4Rs. In this study, we sought to investigate the role of P2 × 4Rs in mediating DA neurotransmission by exploring their impact on DA-dependent behavior, specifically rotation frequency in the unilateral 6-hydroxydopamine-lesioned mouse model of DA-depletion. While we did not observe any differences in the degree of lesioning based on immunostaining for tyrosine hydroxylase between sexes, male mice displayed a greater number of rotations with L-DOPA compared to female mice. In contrast, we observed that IVM plus L-DOPA increased the number of rotations (per 10 min) in female, but not male mice. These findings highlight the potential role of pharmacologically targeting the purinergic receptor system in modulating DA neurotransmission as well as the importance of sex differences impacting outcome measures., Competing Interests: Declaration of Competing Interest There are no declarations of interests to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The focus of gastro-intestinal parasite control in the sheep industry is increasingly on finding a balance between maintaining productivity of the flock whilst minimising selection for anthelmintic resistance to preserve anthelmintic efficacy for the future. Periparturient ewes represent the major source of gastro-intestinal parasites for growing lambs and are therefore a priority for parasite control. This study examines the impact on ewe faecal egg counts (FECs), lamb FECs, lamb daily live weight gains (DLWGs) and pasture larval counts of treating groups of ewes two weeks prior to lambing with either, a long-acting moxidectin treatment, short-acting doramectin or control. Six groups of twenty ewes were allocated to individual paddocks, two groups allocated to each treatment, and weekly faecal sampling was performed throughout from the ewes and from six weeks after the start of lambing in the lambs. Treatment group was found to have a significant effect on both ewe FEC (p<0.001) and lamb FEC (p = 0.001) with the group receiving the long-acting anthelmintic having the lowest ewe and lamb FECs. There was no significant effect on the DLWGs of the lambs. Pasture larval counts at the end of the study period were lowest in the long-acting wormer treatment group. The use of long-acting moxidectin may be helpful as part of a parasite control programme by reducing the worm burdens of ewes and their lambs, decreasing the number of anthelmintic treatments required in that year and by reducing pasture contamination for those sheep which will graze the pasture in the next year. However, like all anthelmintics, its use should be judicious to avoid selection for resistance., Competing Interests: This work was supported by Zoetis UK. This does not alter our adherence to PLOS ONE policies on sharing data and materials

Although there is increasing importance placed on the use of mathematical models for the effective design and management of long-term parasite elimination, it is becoming clear that transmission models are most useful when they reflect the processes pertaining to local infection dynamics as opposed to generalized dynamics. Such localized models must also be developed even when the data required for characterizing local transmission processes are limited or incomplete, as is often the case for neglected tropical diseases, including the disease system studied in this work, viz. lymphatic filariasis (LF). Here, we draw on progress made in the field of computational knowledge discovery to present a reconstructive simulation framework that addresses these challenges by facilitating the discovery of both data and models concurrently in areas where we have insufficient observational data. Using available data from eight sites from Nigeria and elsewhere, we demonstrate that our data-model discovery system is able to estimate local transmission models and missing pre-control infection information using generalized knowledge of filarial transmission dynamics, monitoring survey data, and details of historical interventions. Forecasts of the impacts of interventions carried out in each site made by the models estimated using the reconstructed baseline data matched temporal infection observations and provided useful information regarding when transmission interruption is likely to have occurred. Assessments of elimination and resurgence probabilities based on the models also suggest a protective effect of vector control against the reemergence of LF transmission after stopping drug treatments. The reconstructive computational framework for model and data discovery developed here highlights how coupling models with available data can generate new knowledge about complex, data-limited systems, and support the effective management of disease programs in the face of critical data gaps., Competing Interests: The authors have declared that no competing interests exist.

Background: Recent reports indicated that increasing the monthly oral dosage and the number of consecutive monthly doses of moxidectin improved the efficacy against macrocyclic lactone (ML)-resistant Dirofilaria immitis. The two laboratory studies reported here evaluated the efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of either Heartgard® Plus (ivermectin/pyrantel) or Interceptor® Plus (milbemycin oxime/praziquantel) against ML-resistant D. immitis strains., Methods: Dogs were inoculated 30 days prior to first treatment with 50 third-stage (L 3 ) larvae of a ML-resistant strain of D. immitis, ZoeLA or JYD-34. In each study, dogs (six per group) were randomized to treatment with six monthly doses of placebo, four or six monthly doses of 24 µg/kg moxidectin, or six monthly doses of Heartgard® Plus or Interceptor® Plus at their label dose rates. Efficacy was evaluated by adult heartworm counts approximately nine months after L 3 inoculation., Results: All negative-control dogs were infected with adult heartworms (geometric mean, 35.6; range, 24-41) for ZoeLA and (geometric mean, 32.9; range, 30-37) for JYD-34. Efficacies against ZoeLA for moxidectin, Heartgard® Plus and Interceptor® Plus were ≥ 96.1%, 18.7% and 21.2%, respectively. Adult counts for both moxidectin-treated groups were significantly lower than negative control (P < 0.0001), significantly lower than Heartgard® Plus and Interceptor® Plus (P < 0.0001), but not significantly different from each other (P = 0.5876). Counts for Heartgard® Plus and Interceptor® Plus were not significantly different than negative control (P ≥ 0.2471). Efficacies against JYD-34 were ≥ 95.9%, 63.9% and 54.6% for moxidectin, Heartgard® Plus and Interceptor® Plus, respectively. Counts for all groups were significantly lower than negative control (P ≤ 0.0001). Counts for six monthly doses of moxidectin were significantly lower than those for four monthly doses (P = 0.0470), and the counts for both moxidectin-treated groups were significantly lower than Heartgard® Plus and Interceptor® Plus (P ≤ 0.0002)., Conclusions: Moxidectin administered orally at 24 µg/kg to dogs for four or six consecutive months was ≥ 95.9% effective in preventing the development of two ML-resistant heartworm strains and resulted in significantly fewer adult D. immitis than in dogs treated with Heartgard® Plus or Interceptor® Plus when administered for six consecutive months at their approved label dosages in two laboratory efficacy studies.

Introduction: onchocerciasis is one of the major infectious diseases caused by Onchocerca volvulus. This parasite is responsible for chronic cutaneous and ocular diseases affecting more than 37 million people of whom 99% are in Africa. The study was conducted in the health district of Ntui from June to September 2016 to determine the prevalence of O. volvulus infection after seven years of massive administration of ivermectin., Methods: two cutaneous snips were made at the iliac crests level in volunteers. These tissues were incubated in physiological saline water and were examined for parasitological investigations in the laboratory., Results: a total of 310 participants were randomly selected, of whom 170 (54.8%) were women and 140 (45.1%) were men aged 6 to 83 years, thus giving a sex ratio of 1.2 in favour of women. After parasitological analysis, 26 participants had microfilaraemia, of whom 15 (10.7%) were men and 11 (6.4%) were women. The most infected age group was 16 to 26 years (12.5%). The highest infection rates were found among farmers (11%) and participants living in the village of Essougly (26.6%). No significant differences in prevalence values between the different groups were noted, whatever the parameter considered., Conclusion: the prevalence of onchocerciasis in the health district of Ntui has declined from a hyperendemic to a hypoendemic state after seven years of massive administration of ivermectin. However, careful monitoring of onchocerciasis should be continued to prevent the area from returning to its original hyperendemicity., Competing Interests: The authors declare no competing interests., (Copyright: Estelle Makou Tsapi et al.)

Ivermectin is an antiparasitic drug that has shown also an effective pharmacological activity towards various infective agents, including viruses. This paper proposes an alternative mechanism of action for this drug that makes it capable of having an antiviral action, also against the novel coronavirus, in addition to the processes already reported in literature.

Historic data show that home flea infestations can be managed by treating all animals on the premises with a highly effective flea control product. The use of effective products has also been shown to reduce pruritus and minimize dermatologic lesions in both cats and dogs. Therefore, an in-home study was conducted in West Central Florida USA to evaluate the efficacy of a topically applied selamectin-sarolaner formulation to control fleas in naturally infested cats over a 12-week period. Thirty-seven cats in 21 households were treated once monthly with the selamectin-sarolaner topical solution. In the topical fluralaner treatment (positive control) group, forty-three cats in 20 households were treated once on day 0. A combined total of thirty dogs in both groups were treated once monthly with oral sarolaner. Fleas on cats were counted by flea combing, fleas on dogs were counted using visual area counts and fleas in the indoor premises were assessed using intermittent-light flea traps. Blinded-assessments of feline dermatologic lesions (modified-SCORFAD) were conducted monthly by a boarded-dermatologist and pruritus severity was evaluated by pet owners. Three consecutive monthly treatments of selamectin-sarolaner reduced flea populations on cats by 96.3 % within 7 days and by 100% from week 6 to the end of the 12-week study. The topical application of fluralaner reduced flea populations by 98.1 % within 7 days and efficacy reached 100% by week 12. At the end of the study, fleas were completely eradicated (from cats, dogs and homes) in every home regardless of treatment group. Owner reported cat pruritus was reduced by > 87 % in both treatment groups by week 12. Significant improvements in dermatologic lesion scores (> 81 %) were achieved by both products by the end of the study. Monthly applications of topical selamectin-sarolaner or topical fluralaner to cats living in the heavy flea challenge environment of West Central Florida USA were effective in eradicating flea infestations, reducing pruritus and improving dermatologic lesions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: None declared.

White-tailed deer ( Odocoileus virginianus ) serve as a host for cattle fever ticks ( Rhipicephalus [ Boophilus ] microplus and Rhipicephalus [ Boophilus ] annulatus ; CFTs); therefore, deer are a concern for CFT control programs in southern Texas, US. Systemic (oral delivery of ivermectin) and topical (permethrin on pelage) treatment devices have been developed for white-tailed deer; however, the efficacy of these treatment options has not been determined for CFTs in southern Texas. Our objectives were to evaluate the effectiveness of CFT treatment strategies by 1) measuring exposure rates of deer to the acaricides permethrin and ivermectin, 2) determining the relationship between CFTs on deer and exposure to the acaricides, and 3) determining if photos from remote cameras at medicated bait sites can be used as a measure of acaricide treatment. We captured 327 deer at four sites in southern Texas. Deer visitation to medicated bait sites was monitored using remote cameras from March 2010 to February 2012. There was no relationship between the presence of permethrin and the probability of being infested with CFTs ( P ≥0.336). The probability of infestation with CFTs decreased as serum ivermectin levels increased for male ( n =18, P =0.098) and female ( n =33, P <0.001) deer. Our results indicate ivermectin may be more effective in treating CFTs than permethrin; thus it would be worthwhile to develop topical acaricides other than permethrin for treating white-tailed deer in southern Texas.

Strongyloidiasis is a disease caused by the nematode Strongyloides stercoralis that is endemic in rural regions in tropical and subtropical countries. Immunosuppressed patients have an increased risk of infection by this parasite and are at risk of developing a hyperinfection syndrome which involves a higher risk of death. The syndrome is treated with ivermectin, however, there is no parenteral presentation of this medication for human use in Colombia or the world, which is an important problem in patients who have compromised enteral absorption, for instance, those with intestinal obstructions. We present a case of hyperinfection syndrome by Strongyloides stercoralis in Colombia, which was treated with subcutaneous ivermectin. Our purpose is to encourage pharmacokinetic and pharmacodynamic studies to establish this route of administration in the future as an alternative for those patients who have a high risk of therapeutic failure with the oral route.

In Haiti, 22 communes still require mass drug administration (MDA) to eliminate lymphatic filariasis (LF) as a public health problem. Several clinical trials have shown that a single oral dose of ivermectin (IVM), diethylcarbamazine (DEC) and albendazole (ALB) (IDA) is more effective than DEC plus ALB (DA) for clearing Wuchereria bancrofti microfilariae (Mf). We performed a cluster-randomized community study to compare the safety and efficacy of IDA and DA in an LF-endemic area in northern Haiti. Ten localities were randomized to receive either DA or IDA. Participants were monitored for adverse events (AE), parasite antigenemia, and microfilaremia. Antigen-positive participants were retested one year after MDA to assess treatment efficacy. Fewer participants (11.0%, 321/2917) experienced at least one AE after IDA compared to DA (17.3%, 491/2844, P<0.001). Most AEs were mild, and the three most common AEs reported were headaches, dizziness and abdominal pain. Serious AEs developed in three participants who received DA. Baseline prevalence for filarial antigenemia was 8.0% (239/3004) in IDA localities and 11.5% (344/2994) in DA localities (<0.001). Of those with positive antigenemia, 17.6% (42/239) in IDA localities and 20.9% (72/344, P = 0.25) in DA localities were microfilaremic. One year after treatment, 84% percent of persons with positive filarial antigen tests at baseline could be retested. Clearance rates for filarial antigenemia were 20.5% (41/200) after IDA versus 25.4% (74/289) after DA (P = 0.3). However, 94.4% (34/36) of IDA recipients and 75.9% (44/58) of DA recipients with baseline microfilaremia were Mf negative at the time of retest (P = 0.02). Thus, MDA with IDA was at least as well tolerated and significantly more effective for clearing Mf compared to the standard DA regimen in this study. Effective MDA coverage with IDA could accelerate the elimination of LF as a public health problem in the 22 communes that still require MDA in Haiti., Competing Interests: The authors have declared that no competing interests exist.

Following the halt of mass drug administration (MDA) for lymphatic filariasis (LF), the WHO recommends at least 4 years of post-treatment surveillance (PTS) to confirm that transmission recrudescence or importation does not occur. The primary means of evaluation during PTS is repeated transmission assessment surveys (TASs) conducted at 2- to 3-year intervals after TAS-1 stop-MDA surveys. This study reports the results of TAS-2 and TAS-3 surveys in Plateau and Nasarawa states (pop. 6.9 million) of Nigeria divided into a minimum of seven evaluation units (EUs) per TAS. A total of 26,536 first- and second-year primary school children (approximately 6-7 years old) were tested for circulating filarial antigen (CFA) between 2014 and 2017. Of 12,313 children tested in TAS-2 surveys, only five (0.04%) were CFA positive, with no more than two positive samples from any one EU, which was below the critical value of 20 per EU. Of 14,240 children tested in TAS-3 surveys, none (0%) were CFA positive. These results indicate that LF transmission remains below sustainable transmission levels and suggest that elimination of transmission has been achieved in Plateau and Nasarawa, Nigeria.

A study was conducted in grazing dairy heifers to assess anthelmintic efficacy and production responses in dairy heifers treated with a single injection of eprinomectin in an extended-release formulation over a 123 day-period. The study was conducted on a pasture-based dairy in the Southeastern United States (North Carolina) over the summer months. Sixty crossbred dairy heifers were weighed and randomly allocated into 2 groups. One group (n = 30) was given 5% eprinomectin subcutaneously in the cervical region while the other group (n = 30) was given an equivalent volume of saline. Calves were weighed every 30 days throughout the trial for calculation of average daily gain and differences in overall weight gain. In addition, fecal samples were collected at days 0, 30, 60, 90 and 123 for worm egg count and coproculture. Both groups of cattle had similar worm egg concentrations at the start of the study. However, the control group had increasing concentrations of fecal worm eggs throughout the summer months while the heifers that received eprinomectin had minimal fecal worm eggs. The primary parasite species identified in this study were Haemonchus placei, Cooperia species and Ostertagia. The heifers that received eprinomectin gained 105 + 2.8 kg during the 123-day study period, representing an average daily gain of 0.85 kg/day compared to 78.3 + 4.1 kg (0.64 kg/day) for the control group. This represented a 33 % increase in average daily gain associated with deworming. The results of this study indicate that a single dose of extended-release eprinomectin was sufficient to control parasites through a 123-day summer grazing season and that administration of the anthelmintic had a significant impact on weight gain., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The diagnosis of scabies has become surprisingly frequent in Germany in recent years and the use of scabicides has risen significantly., Objective: The aim of our survey was to determine whether this trend can also be detected among military personnel of the German Armed Forces (Bundeswehr)., Methods: The study was conducted as a retrospective single-center study over a period of 8 years from 2012 to 2019 in the Department of Dermatology of the Armed Forces Hospital Berlin, Germany. Data were generated from the hospital information system (KIS), which was searched for all scabies-coded diagnoses according to ICD10 code B86 both as outpatients and inpatients. Only first presentations with scabies diagnosis confirmed by dermoscopy or microscopy by a dermatologist were included. Inpatient treatment was required if a patient was not cured after at least three antiscabies treatment cycles in the outpatient setting., Results: The data show that there has been a steady increase in the diagnosis of scabies in Bundeswehr personnel. Moreover, our data show that the number of unsuccessfully treated outpatients increased and required in-hospital treatment., Conclusion: We observed an increase of scabies among German military personnel who represent a typical at-risk group. These results support the observations of an increased incidence of scabies in Germany in general and especially in an at-risk population. With the general increase in scabies cases, there are also increasing numbers of German military personnel who are refractory to treatment, which was largely attributed to inadequate treatment of contact persons and individual treatment errors. Nevertheless, the data also emphasize the low overall prevalence of scabies; therefore, all diagnoses should be confirmed by dermoscopy or microscopy after 14 days whenever possible to rule out the bias of overreporting due to false-positive cases diagnosed only by clinical examination.

Background: In recent years, there has been a significant increase in scabies infestations throughout German-speaking countries. Given the high frequency of treatment failures, the question arises as to whether topical permethrin treatment is always performed correctly., Patients and Methods: Our department uses a fluorescent test cream to teach patients on how to correctly apply topical permethrin. In the context of a prospective observational study of 21 patients, we systematically assessed and analyzed potential application errors., Results: None of the participants succeeded in adequately applying the cream to the entire skin as previously instructed. The median number of regions left untreated was six (minimum: 2; maximum: 18), which included a median body surface area of 6 % (minimum: 2 %; maximum: 30 %). With regard to predilection sites of scabies, the ankles were left untreated in 62 % of cases, followed by the interdigital spaces (toes) (33 %) and the sacral region (24 %). All patients considered the pretreatment training to be very useful., Conclusions: The present findings clearly demonstrate potential shortcomings when it comes to the application of topical antiscabies treatment. This may provide a (potentially underestimated) explanation for the large number of reports on treatment failures in this regard, which falsely suggest potential treatment resistance., (© 2020 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

In November 2019 a 5-month-old mixed-breed rabbit presented to Chungbuk National University Veterinary Teaching Hospital, Cheongju-si, Chungbuk, Republic of Korea (Korea) with symptoms comprising pruritus, crusts on skin, poor appetite and reduced defecation. The rabbit was purchased 2 months prior from a pet shop located in a big market, and that the symptoms were first observed about 2 weeks prior to the hospital visit. Physical examination revealed that the patient had crust formation and alopecia on the nose together with lesions on the digits. A skin scraping test was performed using mineral oil and a high density of mites was observed by microscopy. Each mite showed a round, tortoise-like body with 4 comparatively short pairs of legs. The anus was located at the terminal unlike with suspected pathogen, Notoedres cati. Based on morphological characteristics, we identified the mite as Sarcoptes sp. Ivermectin was administered weekly by subcutaneous injection at a dosage of 0.4 mg/kg, and 4 weeks of follow-up study revealed the patient was fully recovered. And no more mites were detected from the case. This is the first case report of sarcoptic mange in a pet rabbit in Korea.

Background: Little information is available on the effect of ivermectin on the third- and fourth-stage larvae of Onchocerca volvulus. To assess a possible prophylactic effect of ivermectin on this parasite, we compared the effects of different ivermectin regimens on the acquisition of onchocercal nodules., Methods: We analyzed data from a controlled randomized clinical trial of ivermectin conducted in the Mbam Valley (Cameroon) between 1994 and 1998 in a cohort of onchocerciasis infected individuals. The number of nodules that appeared between the start and the end of the clinical trial was analyzed, using ANOVA and multivariable Poisson regressions, between four treatment arms: 150 µg/kg annually, 800 µg/kg annually, 150 µg/kg 3-monthly, and 800 µg/kg 3-monthly., Results: The mean number of nodules that appeared during the trial was reduced by 17.7% in subjects treated 3-monthly compared to those treated annually (regardless of the dose). Poisson regression model, adjusting on subject's age and weight, initial number of nodules and intensity of O. volvulus infection in his village of residence, confirmed that the incidence of new nodules was reduced in 3-monthly treatment arms compared to annually treatment arms, and that the dosage of ivermectin does not seem to influence this effect. Furthermore, the number of newly acquired nodules was positively associated with the initial number of nodules. Analysis of disappearance of nodules did not show any significant difference between the treatment groups., Conclusions: To our knowledge, these results suggest for the first time in humans, that ivermectin has a partial prophylactic effect on O. volvulus. Three-monthly treatment seems more effective than annual treatment to prevent the appearance of nodules.

In this work, the anionic and cationic lignin-based drug-loaded materials (SL/CTAB) with strong hydrophobicity were prepared by using Sodium Lignosulfonate (SL) via self-assembly. The obtained SL/CTAB was used as drug-loaded material and emulsifier to prepare avermectin nano-formulation, which can be automatically dispersed into nano drug-loaded nanospheres in water. The cold and hot storage experiments show that the physical and chemical stability of the nano-formulation is good. The nano-formulation exhibits controlled-release performance, and the cumulative release amounts range from 56.27% to 87.33% in 62 h. Meanwhile, the release rates slow down with increasing SL/CTAB dosage. After UV irradiation for 50 h, the retention rates of avermectin in the nano-formulation range from 46.67% to 63.41%, which is 2.18-2.96 times higher than commercial avermectin Emulsifiable Concentrate (EC). The experiment of simulated rainwater scour-resistance shows that the affinity of lignin-based nano-formulation to the Epipremnum aureum leaves is higher than EC formulation., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The safety and efficacy of a new spot-on formulation of selamectin plus sarolaner were evaluated for the treatment and control of natural flea infestations on cats in two non-randomised, multi-centre clinical trials conducted in 8 different locations in Queensland, Australia., Methods: One hundred and four cats from 65 different households were enrolled across the two studies. Demographic characteristics of cats in the two studies were similar. The new spot-on formulation of selamectin and sarolaner was administered topically once a month for 3 consecutive months at a minimum dosage of 6 mg/kg selamectin (dose range 6-12 mg/kg) plus 1 mg/kg sarolaner (dose range 1-2 mg/kg). Cats were dosed on Days 0 (pre-treatment), 30 and 60 and physical examinations and flea counts were conducted on Days 0, 30, 60 and 90. Efficacy assessments were based on the percentage reduction in live flea counts post-treatment compared to Day 0., Results: In Study A, at enrolment, primary cats had flea counts ranging from 6 to 107 (arithmetic mean 21.0). The selamectin and sarolaner spot-on formulation resulted in arithmetic mean efficacy of 98.0%, 100% and 100% on Days 30, 60 and 90, respectively. In Study B, at enrolment, primary cats had flea counts ranging from 6 to 22 (arithmetic mean 10.0). The selamectin and sarolaner spot-on formulation resulted in arithmetic mean efficacy of 99.7%, 100% and 100% on Days 30, 60 and 90, respectively., Conclusions: The new spot-on formulation of selamectin plus sarolaner topically administered at monthly intervals at the minimum dosage of 6.0 mg/kg selamectin and 1.0 mg/kg sarolaner was safe and highly effective against natural infestations of fleas under a range of geographical conditions, representative of both tropical and subtropical regions of Australia.

Vincristine is the first-line drug for the chemotherapy of canine transmissible venereal tumor (CTVT). Drug resistance is related to tumor cyto-morphological patterns of CTVT. There are anti-cancer properties of ivermectin, thus, a combination of ivermectin and vincristine could be an effective chemo-therapeutic treatment regimen for CTVT. Study aims, therefore, were to (1) assess the frequency of CTVT cyto-morphologies, and (2) evaluate treatment efficacy and possible adverse reactions to vincristine compared with a combination vincristine and ivermectin. Dogs (n = 41) with CTVT were characterized by tumor cyto-morphology and disease severity and of those, 20 were randomly allocated into two groups. There was a control group (G-Vin; n = 10) in which there was treatment with vincristine; and an experimental group (G-Iv/Vin; n = 10) in which there was treatment with the ivermectin/vincristine combination. Although dogs in the G-Iv/Vin group had more severe disease at the beginning of the study (P = 0.0031), the number of weeks and chemotherapy sessions until tumor remission were similar among dogs of the two groups, indicating both treatments were effective. There was a decrease in the leukocyte counts (P = 0.0020), related to neutropenia (P = 0.0371) in the G-Vin but not the G-Iv/Vin treatment group. There was no tumor resistance that developed during the study regardless of the treatment regimen used or tumor cytomorphology. In summary, the use of the vincristine/ivermectin combination was well tolerated and efficacious for CTVT treatment., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to report., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Mass administration of antimalarial drugs and ivermectin are being considered as potential accelerators of malaria elimination. The safety, tolerability, pharmacokinetics, and mosquito-lethal effects of combinations of ivermectin, dihydroartemisinin-piperaquine, and primaquine were evaluated. Coadministration of ivermectin and dihydroartemisinin-piperaquine resulted in increased ivermectin concentrations with corresponding increases in mosquito-lethal effect across all subjects. Exposure to piperaquine was also increased when coadministered with ivermectin, but electrocardiograph QT-interval prolongation was not increased. One subject had transiently impaired liver function. Ivermectin mosquito-lethal effect was greater than predicted previously against the major Southeast Asian malaria vectors. Both Anopheles dirus and Anopheles minimus mosquito mortality was increased substantially (20-fold and 35-fold increase, respectively) when feeding on volunteer blood after ivermectin administration compared with in vitro ivermectin-spiked blood. This suggests the presence of ivermectin metabolites that impart mosquito-lethal effects. Further studies of this combined approach to accelerate malaria elimination are warranted., (© 2019 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Ascaris lumbricoides is a common infection, and mainly affects children living in low-income areas. Water and sanitation improvement, health education, and drug treatment may help break the cycle of transmission, and effective drugs will reduce morbidity., Objectives: To compare the efficacy and safety of anthelmintic drugs (albendazole, mebendazole, ivermectin) for treating people with Ascaris infection., Search Methods: We searched the Cochrane Infectious Disease Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, three other databases, and reference lists of included studies, without language restrictions, up to 4 July 2019., Selection Criteria: Randomized controlled trials (RCT) that compared albendazole, mebendazole, and ivermectin in children and adults with confirmed Ascaris infection., Data Collection and Analysis: Two review authors independently assessed studies for inclusion, assessed risk of bias, and extracted data from the included trials. A third review author checked the quality of data extraction. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) to compare dichotomous outcomes in treatment and control groups. We used the fixed-effect model for studies with low heterogeneity and the random-effects model for studies with moderate to high heterogeneity. We assessed the certainty of the evidence using the GRADE approach. We used the control rate average to provide illustrative cure rates in the comparison groups., Main Results: We included 30 parallel-group RCTs, which enrolled 6442 participants from 17 countries across Africa, Asia, Central America and the Caribbean, and South America. Participants were from 28 days to 82 years of age, recruited from school, communities, and health facilities. Twenty studies were funded or co-funded by manufacturers, while 10 studies were independent of manufacturer funding. Twenty-two trials had a high risk of bias for one or two domains (blinding, incomplete outcome data, selective reporting). Single dose of albendazole (four trials), mebendazole (three trials) or ivermectin (one trial) was compared to placebo. Parasitological cure at 14 to 60 days was high in all the studies (illustrative cure of 93.0% in the anthelmintic group and 16.1% in the placebo group; RR 6.29, 95% CI 3.91 to 10.12; 8 trials, 1578 participants; moderate-certainty evidence). Single dose of albendazole is as effective as multiple doses of albendazole (illustrative cure of 93.2% with single dose, 94.3% with multiple doses; RR 0.98, 95% CI 0.92 to 1.05; 3 trials, 307 participants; high-certainty evidence); or as single dose of mebendazole (illustrative cure of 98.0% with albendazole, 96.9% with mebendazole; RR 1.01, 95% CI 1.00 to 1.02; 6 trials, 2131 participants; high-certainty evidence). Studies did not detect a difference between a single dose of albendazole and a single dose of ivermectin (cure rates of 87.8% with albendazole, 90.2% with ivermectin; RR 0.99, 95% CI 0.91 to 1.08; 3 trials, 519 participants; moderate-certainty evidence). Across all the studies, failure after single dose of albendazole ranged from 0.0% to 30.3%, mebendazole from 0.0% to 22.2%, and ivermectin from 0.0% to 21.6%. The egg reduction rate (ERR) measured up to 60 days after the treatment was high in all treated groups, regardless of the anthelmintic used (range 96% to 100%). It was not possible to evaluate parasitological cure by classes of infection intensity. No included trials reported complication or serious adverse events. Other adverse events were apparently similar among the compared anthelmintic groups (moderate- to low-certainty evidence). The most commonly reported other adverse events were nausea, vomiting, abdominal pain, diarrhoea, headache, and fever., Authors' Conclusions: Single-dose of albendazole, mebendazole, and ivermectin all appeared effective against Ascaris lumbricoides infection, yielding high parasitological cure and large reductions in eggs excreted, with no differences detected between them. The drugs appear to be safe to treat children and adults with confirmed Ascaris infection. There is little to choose between drugs and regimens in terms of cure or adverse events., (Copyright © 2020 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Introduction: Onchocerciasis is an infection caused by Onchocerca volvulus . It affects 37 million people of which 99% are in Africa. This study assessed the prevalence of onchocerciasis after 15 years of mass drug administration with ivermectin., Methods: This was a population based cross sectional study. Questionnaires covering participants' identity and attitudes and practices of community respondents towards ivermectin were administered. The treatment coverage was obtained by review of records of mass drug administration from 1999 to 2015. The epidemiological evaluation of infection status was done by parasitological examination of skin snips and nodule palpation in individuals in five health areas of the district., Results: A total of 400 participants were randomly selected. Of these, 56.0% were males, 62.0% single, 59.5% farmers and 98.0% Christians. Participants with good attitudes towards community directed treatment with ivermectin made up 80.5% while 47.8% of the participants had good practice. The highest treatment coverage achieved was 88.0% in 2010 while lowest was 57.0% in 2002. Less than 2% had microfilaria and 6.0% had nodules. There was no statistically significant difference in the prevalence of microfilaria with respect to age. There was a statistically significant difference in the distribution of nodules (χ 2 =73.6, p=0.001) among the different age groups. The greatest rate of infection (2.1%) was among farmers., Conclusion: This study showed that the prevalence reduced compared to other prevalence studies in Cameroon. The study area was hypo-endemic for onchocerciasis., Competing Interests: The authors declare no competing interests., (© Sharon Mumah Nyagang et al.)

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., Competing Interests: Declaration of Competing Interest All authors declare that there are no conflicts of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)